A review: Pancreatic enzymes in the treatment of chronic pancreatic insufficiency in companion animals.

The purpose of this review was to analyze the scientific literature on exocrine pancreatic insufficiency (EPI) in dogs and cats and our own research on porcine model to compare animal- and microbial-derived enzymes in the treatment of animals with this disease. Clinical signs of EPI occur when more than 85% of the pancreatic parenchyma is non-functional. EPI can be a consequence of various diseases. The insufficient activity or deficiency of pancreatic enzymes leads to impaired digestion and absorption, and consequently, to malnutrition. The primary treatment for enzyme insufficiency is pancreatic enzyme replacement therapy (PERT). PERT in animals with EPI is a lifetime therapy. Most commercially available products are of animal origin (processed pancreata obtained from a slaughter house) and contain lipases, alpha-amylase, and proteases. Enzymes of microbial and plant origin seem to be a promising alternative to animal-derived enzymes, but to date there are no registered preparations containing all enzymes simultaneously for use in clinical practice to treat EPI. Results from some previous studies have highlighted the "extra-digestive" functions of pancreatic enzymes, as well as the actions of pancreatic-like microbial enzymes. For example, trypsin activates protease-activated receptor and provokes maturation of enterocytes and enterostatin inhibits fat absorption. It has been postulated that intrapancreatic amylase is the main component of the acini-islet-acinar axis-the reflex which down regulates insulin release, while gut and blood amylase exhibit anti-incretin actions "per se." Additionally, high but still physiological blood amylase activity coincide with physiological glucose homeostasis and a lack of obesity.

Anti-Incretin Gut Features Induced by Feed Supplementation with Alpha-Amylase: Studies on EPI Pigs.

The acini-islet-acinar (AIA) axis concept justifies the anatomical placement of the Langerhans islets within the exocrine pancreatic parenchyma and explains the existence of the pancreas as a single organ. Amylase has been suggested to play a key role as an anti-incretin factor. Oral glucose tolerance tests (OGTT) were performed on 18 piglets in both a healthy (prior to pancreatic duct ligation (PDL) surgery, study Day 10) and an exocrine pancreatic insufficient (EPI) state (30 days after PDL, study Day 48)). Amylase (4000 units/feeding) or Creon® (100,000 units/feeding) was administered to pigs with the morning and evening meals, according to study design randomization, for 37 days following the first OGTT. Blood glucose levels, as well as plasma levels of insulin, GLP-1, and GIP, were measured, and the HOMA-IR index was calculated. EPI status did not affect the area under the curve (AUC) of insulin release, fasting insulin levels, or the HOMA-IR index, while amylase supplementation led to a significant (p < 0.05) decrease in the above-mentioned parameters. At the same time, EPI led to a significant (p < 0.05) increase in GLP-1 levels, and neither amylase nor Creon® supplementation had any effects on this EPI-related increase. Fasting plasma levels of GIP were not affected by EPI; however, the GIP response in EPI and Amylase-treated EPI animals was significantly lower (p < 0.05) when compared to that of the intact, healthy pigs. Orally administered amylase induces gut anti-incretin action, normalizing glucose homeostasis and reducing HOMA-IR as a long-term outcome, thus lowering the risk of diabetes type II development. Amylase has long-lasting anti-incretin effects, and one could consider the existence of a long-lasting gut memory for amylase, which decreases hyperinsulinemia and hyperglycemia for up to 16 h after the last exposure of the gut to amylase.

Potential of Bacterial Cellulose in Reconstructive Surgery of Body Integumentary System: Preliminary Studies in Animals.

The aim of the study is to present the preliminary results of the in vivo application of Komagataeibacter xylinum E25 bacterial cellulose (BC) as a replacement material for produced defects during operations. Three pigs (sus scrofa domestica) had the same defects in the ear cartilage (4 × 4 cm) and in the rectus abdominis muscle (6 × 10 cm) with BC membranes implanted into them. The time of observation of the condition of the animals was 3 months. Implantation sites did not show clinical signs of complications in the form of inflammation or necrosis. Histologically, a normal scar was produced as a result of the material healing into the host's body. In one case, no residual implant material was found at the site of implantation, and the remodeled scar confirmed healing. No systemic inflammatory reaction was observed in any of the animals. The host organism's reaction to the bacterial cellulose allows us to believe that it meets the expectations as a material that can be widely used in reconstructive surgery. Nevertheless, this requires further research on a larger group and also using other foreign bodies. The next step would be an experiment on a group consisting of people.

Milk Formula Enriched with Sodium Butyrate Influences Small Intestine Contractility in Neonatal Pigs.

Butyrate, a by-product of gut bacteria fermentation as well as the digestion of fat in mother's milk, exerts a wide spectrum of beneficial effects in the gastrointestinal tissues. The present study aimed to determine the effects of sodium butyrate on small intestine contractility in neonatal piglets. Piglets were fed milk formula alone (group C) or milk formula supplemented with sodium butyrate (group B). After a 7-day treatment period, isometric recordings of whole-thickness segments of the duodenum and middle jejunum were obtained by electric field stimulation under the influence of increasing doses of Ach (acetylocholine) in the presence of TTX (tetrodotoxin) and atropine. Moreover, structural properties of the intestinal wall were assessed, together with the expression of cholinergic and muscarinic receptors (M1 and M2). In both intestinal segments (duodenum and middle jejunum), EFS (electric field stimulation) impulses resulted in increased contractility and amplitude of contractions in group B compared to group C. Additionally, exposure to dietary butyrate led to a significant increase in tunica muscularis thickness in the duodenum, while mitotic and apoptotic indices were increased in the middle jejunum. The expression of M1 and M2 receptors in the middle jejunum was significantly higher after butyrate treatment. The results indicate increased cholinergic signaling and small intestinal growth and renewal in response to feeding with milk formula enriched with sodium butyrate in neonatal piglets.

The Impact of Sleep-Disordered Breathing on Ghrelin, Obestatin, and Leptin Profiles in Patients with Obesity or Overweight.

BACKGROUND: The impact of concomitant obesity and sleep disorders on neuropeptides related to energy balance is poorly understood. The aim of this study was to assess the nocturnal profile of total ghrelin, obestatin, and leptin in patients with elevated BMI and to investigate the impact of breathing-related sleep disorders on these hormone levels. METHODS: The study involved 58 patients with suspicion of obstructive sleep apnea (OSA). Patients underwent anthropometric and sleep examination and measurements of night ghrelin, leptin, and obestatin levels. RESULTS: In patients with OSA (n = 46), recognized on the basis of sleep examination outcomes, the correlation of anthropometric measurements with parameters of sleep disorders and ghrelin levels was observed, contrary to the control group (n = 12). In the OSA group, levels of ghrelin were significantly lower than in the control group at 5:00 and 7:00. Levels of leptin in the OSA group were also lower than those in the control groups (not statistically significant). Profiles of obestatin in both groups were similar. CONCLUSIONS: Our results confirm the relationship between obesity and sleep-disordered breathing. Both these disorders affect ghrelin levels-parameters of obesity negatively correlate with hormone concentration, and OSA seems to lower ghrelin values in the second half of the night.

Pre-digestion of the lipids in infant formula affects gut maturation of the preterm pig.

Preterm birth is associated with increased risk of complications, specifically with regards to the gastrointestinal tract. These complications mainly include the maldigestion and malabsorption of nutrients resulting from the immaturity of the small intestine. The current study investigated whether pre-digestion of fat in infant formula would affect the developmental remodeling of the structure of the small intestine mucous membrane. Three groups of premature piglets (corresponding to 30-32 week of human gestation) were used in the study: the first group, not subjected to any treatment and euthanized within 2 hours after caesarian delivery, was used as the control group (PT group), the second group, was fed an infant formula-IF (SPT group), and the third group was fed a lipase pre-hydrolyzed infant formula-hIF (PPT group). Feeding preterm piglets with an infant formula for 14 days stimulated intestinal maturation (in SPT and PPT groups). However, pre-digestion of the infant formula with lipase significantly increased proliferative activity and intensity of apoptosis in the small intestine epithelium, resulting in more rapid enterocyte turnover. The data obtained not only confirm that starting enteral feeding directly after birth stimulates developmental and structural changes in the small intestine, but also highlighted the importance of lipid digestion for enterocyte turnover and speeding up of intestinal maturation in preterm piglets. The latest is of high importance for the proper gut development of preterm children.

The Effectiveness of a Bioactive Healing Abutment as a Local Drug Delivery System to Impact Peri-Implant Mucositis: A Prospective Case Series Study.

Modern dental therapy makes use of prosthetic implant reconstructions, which are supported or retained on dental implants. The most frequent, long-term complications associated with these prosthetic implants include mucositis and peri-implantitis. Since mucositis is the initial inflammation of tissues supporting the dental implant, the management of this condition is thus crucial. The aim of the present study was to assess the effects of the placement of bioactive healing abutment for 48 h, in patients diagnosed with peri-implant mucositis. Moreover, the quantitative and qualitative shift in the bacterial profile of the biofilm present in the peri-implant pockets, was assessed by means of RT-PCR genotyping. Each patient was examined using a commercially available PET test protocol: the first sample was taken upon diagnosis (after which the bioactive healing abutment, with clindamycin at a dose of 30 mg, was used for 48 h and replaced with the prosthetic superstructure used so far by a patient); the second sample was taken two weeks after removal of the bioactive healing abutment. The effects of the intervention were clinically assessed using the PET test after the two weeks. A significant reduction in mucositis was observed following treatment, as measured by periodontal indices: modified Sulcus Bleeding Index­mBI (p < 0.001), modified Plaque Index­PLI (r = 0.69, Z= −4.43; p < 0.001) and probing depth­PD (Z = −4.61; p < 0.001). Significant differences in the occurrence of periopathogenic bacteria were also observed: Aggregatibacter actinomycetemcomitans (p < 0.014; Z = −2.45; r = 0.38), Treponema denticola (p < 0.005; Z = −2.83; r = 0.44), Tannerella forsythia (p < 0.001; Z = −4.47; r = 0.69) and Porphyromonas gingivalis (p < 0.132; Z = −1.51).

Associations of Obstructive Sleep Apnea, Obestatin, Leptin, and Ghrelin with Gastroesophageal Reflux.

Gastroesophageal reflux disease (GERD) is commonly observed in patients with obstructive sleep apnea (OSA). Hormonal disorders observed in OSA may be relevant in the development of GERD. The aim of the study was to assess the correlations between ghrelin, obestatin, leptin, and the intensity of GERD in patients with OSA. The study included 58 patients hospitalized due to clinical suspicion of sleep disorders during sleep. All patients underwent a sleep study, and blood samples were collected overnight for hormonal tests. Survey data concerning symptoms of GERD, gastroscopy, and esophageal pH monitoring results were included in the study. In patients with OSA, GERD was twice as common when compared to the group without OSA. Among subjects with severe sleep apnea (AHI > 30; n = 31; 53%), we observed lower ghrelin levels, especially in the second half of the night and in the morning (p5.00 = 0.0207; p7.00 = 0.0344); the presence of OSA had no effect on obestatin and leptin levels. No significant differences in hormonal levels were observed between the groups depending on the diagnosis of GERD. However, correlations of ghrelin levels with the severity of esophagitis, leptin and ghrelin levels with the severity of GERD symptoms, and leptin levels with lower esophageal pH were found. GERD is more frequent among patients with OSA. In both GERD and OSA, deviations were observed in the levels of ghrelin and leptin. However, our analysis demonstrates that the relationship between OSA and GERD does not result from these disorders.

Maternal High-Fat Diet Exposure During Gestation and Lactation Affects Intestinal Development in Suckling Rats.

Maternal health and diet influence metabolic status and play a crucial role in the development of metabolic function in offspring and their susceptibility to metabolic diseases in adulthood. The pathogenesis of various metabolic disorders is often associated with impairment in intestinal structure and function. Thus, the aim of the current study was to determine the effects of maternal exposure to a high fat diet (HFD), during gestation and lactation, on small intestinal growth and maturation in rat pups at 21 days old. Female, Wistar Han rats were fed either a breeding diet (BD) or high fat diet (HFD), from mating until the 21st day of lactation. Maternal HFD exposure increased body weight, BMI and adiposity. Compared to the maternal BD, HFD exposure influenced small intestine histomorphometry in a segment-dependent manner, changed the activity of brush border enzymes and had an impact on intestinal contractility via changes in cholinergic signaling. Moreover, offspring from the maternal HFD group had upregulated mRNA expression of cyclooxygenase (COX)-2, which plays a role in the inflammatory process. These results suggest that maternal HFD exposure, during gestation and lactation, programs the intestinal development of the offspring in a direction toward obesity as observed changes are also commonly reported in models of diet-induced obesity. The results also highlight the importance of maternal diet preferences in the process of developmental programming of metabolic diseases.

Difference in Performance of EPI Pigs Fed Either Lipase-Predigested or Creon®-Supplemented Semielemental Diet.

Pancreatic enzyme replacement therapy (PERT) and fat predigestion are key in ensuring the optimal growth of patients with cystic fibrosis. Our study attempted to highlight differences between fat predigestion and conventional PERT on body composition of young pigs with exocrine pancreatic insufficiency (EPI). EPI and healthy pigs were fed with high-fat diet for six weeks. During the last two weeks of the study, all pigs received additional nocturnal alimentation with Peptamen AF (PAF) and were divided into three groups: H-healthy pigs receiving PAF; P-EPI pigs receiving PAF+PERT; and L-EPI pigs receiving PAF predigested with an immobilized microbial lipase. Additional nocturnal alimentation increased the body weight gain of EPI pigs with better efficacy in P pigs. Humerus length and area in pigs in groups L and P were lower than that observed in pigs in group H (p value 0.005-0.088). However, bone mineral density and strength were significantly higher in P and L as compared to that of H pigs (p value 0.0026-0.0739). The gut structure was improved in P pigs. The levels of neurospecific proteins measured in the brain were mainly affected in P and less in L pigs as compared to H pigs. The beneficial effects of the nocturnal feeding with the semielemental diet in the prevention of EPI pigs' growth/development retardation are differently modified by PERT or fat predigestion in terms of growth, bone properties, neurospecific protein distribution, and gut structure.

The Anatomical Conditions of the Alveolar Process of the Anterior Maxilla in Terms of Immediate Implantation-Radiological Retrospective Case Series Study.

The feasibility and the level of difficulty of immediate flapless implantation depend largely on the residual alveolar bone. The purpose of the study was to determine how often immediate flapless implantation in the anterior maxilla is feasible and assess the difficulty level using cone-beam computed tomography (CBCT) scans. A radiological retrospective case series study was conducted. In total, 1200 CBCT scans from 300 consecutive patients were analyzed with dedicated planning software. Immediate flapless implants were possible in 78.33% of cases. Drilling direction was either through the apex or the palatal slope. Bimodal was conducted in 9% of the cases; only through the apex in 13.08% of the cases and in 56.25% only in the slope. In 21.67%, immediate flapless implants were excluded. The feasibility and degree of difficulty differed statistically to the disadvantage of the lateral incisors compared to the central incisors. Drilling direction caused that BASE classification reflects the difficulty level of immediate implantation. CBCT is a helpful diagnostic tool for assessing the feasibility of immediate flapless implants due to the residual bone shape and volume. BASE classification helps to determine a challenge level that may also facilitate communication and result in comparison. The alveolar bone condition allows for immediate flapless implants in most cases in the aesthetic region of the maxilla, but they should be performed by an experienced specialist with regard to the bone and soft tissue quality.

Maternal Immunoglobulins in Infants-Are They More Than Just a Form of Passive Immunity?

In the present review, we highlight the possible "extra-immunological" effects of maternal immunoglobulins (Ig) transferred to the blood circulation of offspring, either via the placenta before birth or via the colostrum/milk across the gut after birth in different mammalian species. Using the newborn pig as a model, since they are naturally born agammaglobulinemic, intravenously (i.v.) infused purified serum Ig rapidly improved the vitality, suckling behavior, and ensured the survival of both preterm and term piglets. In further studies, we found that proper brain development requires i.v. Ig supplementation. Studies have reported on the positive effects of i.v. Ig treatment in children with epilepsy. Moreover, feeding newborn pigs an elementary diet supplemented with Ig improved the gut structure, and recently a positive impact of enteral or parenteral Ig supplementation on the absorption of polyunsaturated fatty acids (PUFAs) was observed in the newborn pig. Summarized, our own results and those found in the literature, indicate the existence of important extra-immune effects of maternal Ig, in addition to the classical protective effects of transferred maternal passive immunity, including effects on the development of the brain, gut, and possibly other organ systems in the neonate. These additional properties of circulating Ig could have an impact on care guidelines for human neonates, especially those born prematurely with low plasma Ig levels.

Correction: The effects of intra-stomach obestatin administration on intestinal contractility in neonatal piglets fed milk formula.

[This corrects the article DOI: 10.1371/journal.pone.0230190.].

Preliminary Clinical Data and the Comparison of the Safety and Efficacy of Autogenous Bone Grafts Versus Xenograft Implantations in Vertical Bone Deficiencies Before Dental Implant Installation.

Two different techniques of vertical bone augmentation were compared to apply them to immunocompromised patients. One of them used autogenous bone graft; the other used xenograft. Thirty patients were involved in the study. Fifteen received autogenous ring shape grafts harvested from the mental region, and 15 received xenograft vertical tunnel augmentation. They have a total of 60 implants placed in the posterior region of the mandible (2 for each patient). Fixed full ceramic crowns were delivered. Two-year follow-up appointments after implant placement were made. Both autogenous bone grafts and xenografts showed similar long-term clinical regeneration outcome of vertical bone defects. Using autogenous bone rings simultaneously fixed by dental implants, the total treatment time and cost were shortened, but the traumatic reactions and complication rates were higher when compared to xenograft vertical tunnel augmentation. Due to the less traumatic character of the procedure, smaller complication rates and higher safety for the patients receiving chronic immunosuppression should avoid bone block augmentation and reap the benefits from vertical tunnel bone augmentation using xenograft materials.

New Surgical Technique Using Xenograft as a Microinvasive Method to Avoid Extensive Bone Reconstruction in Patients With Compromised General Health: Promising Surgical Methodology and First Clinical Results.

The innovative microinvasive immediate implantation technique of dental implants insertion was described. The technique uses bovine xenograft material to restore the bone defect resulting from teeth pathologies and subsequent extraction. Ten patients had extractions of their premolar upper teeth and immediate implantations with xenograft socket augmentation. This unique procedure allowed primary stability of implant above 70 implant stability quotient in all cases. All of the implants healed without complications and were restored with screwed ceramic crowns. Two-year uneventful follow-ups confirmed alveolar xenograft condensation technique as a microinvasive and safe technique, especially for patients with compromised general health who may not undergo complicated restorative operations.

The effects of intra-stomach obestatin administration on intestinal contractility in neonatal piglets fed milk formula.

A 23-amino acid peptide named obestatin is derived from the ghrelin gene. The aim of the experiment was to study the effects of enteral obestatin administration for a 6-day period on intestinal contractility in piglets fed milk formula. Pigs were treated with 0.9% NaCl (group C) or varying doses of obestatin: 2 µg/kg body weight (BW) (group O2), 10 µg/kg BW (O10) or 15 µg/kg BW (O15) every 8 hours via a stomach tube. Blood was sampled for assessment of obestatin concentration. Duodenal and middle jejunum whole-thickness preparations were studied in an organ bath for isometric recording under electric field stimulation (EFS) and increasing doses of acetylcholine (ACh), and in the presence of atropine and tetrodotoxin (TTX). Additionally, the measurement of intestinal muscularis layer and the immunodetection of Muscarinic Acetylcholine Receptors (M1 and M2) were performed. In comparison to C animals, the obestatin concentration in blood plasma was significantly increased in groups O10 and O15. In both studied intestinal segments, significant increases in the frequency and amplitude of spontaneous contractions were observed in O15 and C groups. In the duodenum and middle jejunum significant differences in responsiveness to EFS (0.5, 5 and 50 Hz) were observed between the groups. The addition of 10-4 M ACh to the duodenum significantly increased the responsiveness in tissues. In contrast, in the middle jejunum a significant increase in the amplitude of contraction was observed after the addition of 10-9 and 10-6 M ACh (groups O15 and O10, respectively). Pretreatment with atropine and TTX resulted in a significant decrease in the responsiveness of the intestinal preparations from all groups, in both studied segments. The increased contractility was not dependent on the expression of muscarinic receptors. Results indicate the importance of enteral obestatin administration in the regulation of intestinal contractility in neonatal piglets.

Absorption of Polyunsaturated Fatty Acid (PUFA) Is Related to IgG Blood Levels of Neonatal Pigs during the First 48 Hours Postpartum.

The current study is aimed at highlighting the impact of enterally or parenterally applied immunoglobulins (Igs) on polyunsaturated fatty acid (PUFA) absorption in newborn pigs. Piglets were chosen as the appropriate model since they are born agammaglobulinemic and any effects of Ig addition can thus be easily monitored. Twenty-one, new born piglets were used in the study. Plasma levels of PUFAs, ARA, DHA, and EPA dropped (similarly to that seen in human infants) by between 40 and 50% in newborn, unsuckled piglets fed an infant formula for 48 h. However, piglets fed the same infant formula but supplied with immunoglobulins (Igs) either orally, by feeding piglets with swine or bovine colostrum, or intravenously, by i.u.a. (intraumbilical artery) infusion of swine or human Ig preparations or swine serum, demonstrated improved growth and PUFA levels similar to those observed at birth. The significant positive correlation was found between the body weight gain, as well as levels of ARA and EPA, and plasma immunoglobulins concentration. These results indicate the importance of the presence of Ig in the blood for appropriate absorption of dietary PUFAs and probably other nutrients in newborn piglets. This may have an impact on the dietary guidelines for human neonates, especially those born prematurely with low plasma Ig levels, since PUFAs are important factors for brain development in early life.

Glucose homeostasis dependency on acini-islet-acinar (AIA) axis communication: a new possible pathophysiological hypothesis regarding diabetes mellitus.

Studies have highlighted the existence of two intra-pancreatic axes of communication: one involved in the regulation of enzyme production by insulin-the insular-acinar axis; and another involved in the regulation of insulin release by pancreatic enzymes-the acini-insular axis. Previous studies by our laboratory show that pancreatic enzymes can affect blood glucose homeostasis and insulin secretion independently of their digestive functions, both from the gut lumen and probably from the blood. As a result we would like to introduce here the concept of acini-islet-acinar (AIA) axis communication (feedback), which could play an important role in the development of obesity and diabetes type 2. The AIA feedback links the endocrine and exocrine parts of the pancreas and emphasizes the essential role that the pancreas plays, as a single organ, in the regulation of glucose homeostasis by amylase most probably in gut epithelium and by insulin and glucagon in peripheral blood.

Small intestinal development in suckling rats after enteral obestatin administration.

This study investigated the effect of enteral administration of obestatin on the development of small intestine, as well as oxidative stress markers and trancriptomic profile of gastrointestinal genes. Suckling rats were assigned to 3 groups treated with: C-saline solution; OL-obestatin (125 nmol/kg BW); OH-obestatin (250 nmol/kg BW) administered twice daily, from the 14th to the 21st day of life. Enteral administration of obestatin in both studied doses had no effect neither on the body weight of animals nor the BMI calculated in the day of euthanasia. Compared to the control group (C), treatment with obestatin resulted in significant changes in the histometry of the small intestinal wall as well as intestinal epithelial cell remodeling. The observed changes and their possible implications for intestinal development were dependent on the dosage of peptide. The enteral administration of high dose (OH) of obestatin significantly decreased its expression in the stomach and increased markers of oxidative stress. The gene profile revealed MAPK3 (mitogen-activated protein kinase-3) as the key regulator gene for obestatin action in the gastrointestinal track. In conclusion, we have showed that enteral administration of obestatin influences the gut mucosa remodeling. It is also suggested that the administration of high dose (OH) has inhibitory effect on the intestinal maturation of suckling rats.

The inverse relationship between blood amylase and insulin levels in pigs during development, bariatric surgery, and intravenous infusion of amylase.

The purpose of this research is to explore the link between plasma amylase and insulin levels in growing pigs. Blood was obtained from piglets ranging in age from preterm (8 days to full gestation period), up to postnatal day 90 (2 months post-weaning) that underwent either duodenal-jejunal bariatric interposition surgery or a sham-operation. Plasma amylase activities in preterm and full-term neonates ranged between 500-600 U/L and were decreased by 50% two months post-weaning. Preprandial insulin and C-peptide levels in neonate piglets were not detectable, however they rose gradually after weaning. An increase in plasma amylase activity was observed in the young pigs that underwent duodenal-jejunum bypass (metabolic) surgery. The increase in blood pancreatic amylase activity after an intravenous amylase infusion lowered the subsequent glucose-stimulated insulin/C-peptide release. We suggest a role for blood amylase in the regulation of glucose homeostasis after observing high blood amylase levels in neonate pigs, in pigs that underwent metabolic surgery, and as a result of the reduced glucose-stimulated insulin response following intravenous amylase administration. Blood amylase level is a dynamic physiological parameter, which is not merely a consequence of exocrine pancreatic digestive enzyme production, but rather a regulated factor involved in glucose assimilation and prandial insulin regulation.