Urinary liver-type fatty acid-binding protein in two dogs with acquired Fanconi syndrome: A case report.

Background: Fanconi syndrome (FS) is defined as multiple defects of the proximal tubules and is diagnosed by clinical symptoms. However, in dogs with FS, the damage in the proximal tubules that is responsible for the clinical symptoms has not been evaluated. Among FS cases, tubular damage in acquired FS is reversible following the elimination of a causative factor. Liver-type fatty acid-binding protein (L-FABP) is a biomarker of tubular damage in various animals including dogs. Urinary L-FABP measurement may be useful for the diagnosis and follow-up evaluation in canine FS. Case Description: At the first visit, two Toy Poodles that had no remarkable findings on physical examination presented with glycosuria without hyperglycemia, hypokalemia, hyperchloremia, increased levels of plasma alkaline phosphatase, and metabolic acidosis. Considering all the factors involved, the dogs were clinically diagnosed with acquired FS. The owner reported that they routinely fed the dog with chicken jerky, a recently considered cause of acquired FS. Following the withdrawal of the jerky, abnormalities including glycosuria improved in both dogs. Moreover, urinary L-FABP levels, which were high at diagnosis, presented a decreasing trend during the follow-up. However, in one dog, the elevated urinary L-FABP level did not return to normal. Conclusion: Although the clinical symptoms of acquired FS in dogs could be improved by the elimination of a causative factor, the severity of tubular damage described by urinary L-FABP may not be necessarily linked to the degree of functional deterioration. Therefore, the evaluation of proximal tubular damage by L-FABP may be of clinical value during the follow-up of acquired FS in canines.

Transient postoperative glycosuria after isoflurane exposure in two dogs.

The present report describes two surgical cases involving the development of sudden glycosuria after isoflurane anaesthesia, despite the dogs having normal blood glucose levels and renal glucose reabsorption. The glycosuria manifested 1 day after surgery and resolved spontaneously within 2 days in both cases. Considering that the surgeries (subcutaneous mandibular mass removal and fracture repair) were unrelated to the kidneys, and there were no remarkable events during anaesthesia, the glycosuria may have been associated with the isoflurane anaesthesia. There have been several previous reports of glycosuria in human patients following transient proximal tubule dysfunction due to volatile anaesthetics. This case report suggests the possibility of transient renal dysfunction following isoflurane anaesthesia in these two clinically healthy dogs. However, considering the observational nature of this report, it can not be excluded that any other procedure performed in these animals was responsible of the observed glycosuria.

Comparison of clinicopathological patterns of renal tubular damage in dogs with acute kidney injury caused by leptospirosis and other aetiologies.

In humans, leptospiral acute kidney injury (AKI) is characterised by tubulointerstitial involvement and renal electrolyte losses, impacting clinical presentation and case management. The aim of this study was to evaluate urine chemistry findings in dogs with leptospirosis in order to identify characteristic patterns of tubular damage associated with this disease. Dogs with intrinsic AKI caused by leptospirosis and by other aetiologies were prospectively enrolled. Clinical and clinicopathological variables, including serum and urine chemistry, fractional excretion (FE%) of electrolytes, and urinary neutrophil gelatinase-associated lipocalin (NGAL), were evaluated in both groups and compared statistically. Dogs with leptospirosis (n = 38) had significantly higher serum creatinine concentration than dogs with AKI caused by other aetiologies (n = 37). Serum potassium and glucose concentrations were comparable between groups. Dogs with leptospiral AKI had significantly higher FE of potassium (median 100%, range 20-480 vs. median 68%, range 5-300; P = 0.048), as well as higher magnitude of glucosuria (urine glucose to creatinine ratio, median 0.64, range 0-26 vs. median 0.22, range 0-13; P = 0.023) and frequency of positive glucose dipstick reaction (59% vs. 18%; P = 0.002), than dogs with AKI of other aetiologies. Additional markers of tubular damage considered in this study, including FE of other electrolytes and urinary NGAL, did not differ between groups. In conclusion, when compared to other aetiologies of intrinsic AKI, canine leptospirosis was characterised by increased glucosuria and kaliuresis.

Urine glucose concentration: A useful parameter as a surrogate for glycaemia on the first day of life in canine neonates.

INTRODUCTION: Hypoglycaemia is a well-known risk factor in neonatal puppies and kittens; glycaemia control is crucial during the first days of life. Kidneys immaturity provokes the presence of physiological glycosuria during the first 2-3 weeks of life in small animals. OBJECTIVES: The aim of this study was to evaluate the potential of glycosuria as a predictor of glycaemia in neonatal puppies during the first two weeks of life. METHODS: Prospective study. Thirty-three client-owned healthy neonatal puppies admitted to the Veterinary Teaching Hospital, Autonomous University of Barcelona, were included in the study and divided into four different groups according to the day of sampling (1, 4, 7, and 11 days post-delivery). Glucose levels in blood and urine samples were evaluated and compared between groups. Correlation between glucose levels in blood and urine was also determined. RESULTS: Hypoglycaemia was diagnosed in 17.14% of the puppies and only on day 1 after delivery. A positive and significant correlation between blood and urine glucose concentration on day 1 after delivery was observed. No significant correlation between blood and urine glucose was observed on days 4, 7 and 11 after delivery. CONCLUSIONS: Urine concentration of glucose is a useful parameter to establish glycaemic status on the first day of life in canine puppies.

Basal glucose excretion in dogs: The impact of feeding, obesity, sex, and age.

BACKGROUND: The urine glucose (UG) measurements are an integral part of urinalyses, especially in dogs with polyuria and polydipsia. A positive dipstick result is considered pathologic for disease. This paradigm has been challenged by new ultrasensitive tests, where the manufacturers recommend tolerating slightly positive results. It implies that, as in other species, basal urine glucose losses can exceed the lower limits of detection using ultrasensitive glucose dipsticks in healthy dogs. OBJECTIVES: We aimed to determine whether glucose is routinely detectable using a sensitive quantitative wet chemistry method in the urine of nondiabetic, nonazotemic dogs, and investigate the impact of food intake, obesity, sex, castration status, and age. METHODS: Serial UG measurements were performed in healthy clinic-owned Beagle dogs that were randomly fasted or fed. Glucose was measured in morning urine samples from normal-weight healthy and obese dogs, and the university's electronic database was searched for quantitative UG measurements (Gluco-quant Enzyme Kit/Roche Diagnostics). RESULTS: Small amounts of glucose were detected in 555 (99.1%) of 560 urine samples analyzed. All urine samples from the clinic-owned Beagle dogs, as well as from privately owned obese and normal-weight healthy dogs that tested positive for glucose. The median (range) UG concentration obtained from the university's electronic database was 0.39 (0-1.55) mmol/L, and 2.2% of the samples tested negative. Feeding, obesity, gender, castration status, and age did not affect UG concentrations. CONCLUSIONS: Studies, including a larger number of healthy dogs, are warranted to define a cut-off between physiologic and pathologic glucosuria.

Effect on urine specific gravity of the addition of glucose to urine samples of dogs and cats.

OBJECTIVE: To evaluate effects of the addition of glucose to dog and cat urine on urine specific gravity (USG) and determine whether glucosuria affects assessment of renal concentrating ability. SAMPLE: Urine samples from 102 dogs and 59 cats. PROCEDURES: Urine for each species was pooled to create samples with various USGs. Glucose was added to an aliquot of each USG pool (final concentration, 2,400 mg/dL), and serial dilutions of the glucose-containing aliquot were created for each pool. The USG then was measured in all samples. The difference in USG attributable to addition of glucose was calculated by subtracting the USG of the unaltered sample from the USG of the sample after the addition of glucose. The relationship between the difference in USG and the USG of the unaltered, undiluted sample was evaluated by the use of linear regression analysis. RESULTS: Addition of glucose to urine samples increased the USG. There was a significant relationship between USG of the undiluted sample and the difference in USG when glucose was added to obtain concentrations of 300, 600, 1,200, and 2,400 mg/dL in canine urine and concentrations of 600, 1,200, and 2,400 mg/dL in feline urine. The more concentrated the urine before the addition of glucose, the less change there was in the USG. Changes in USG attributable to addition of glucose were not clinically important. CONCLUSIONS AND CLINICAL RELEVANCE: Substantial glucosuria resulted in minimal alterations in specific gravity of canine and feline urine samples. Thus, USG can be used to assess renal concentrating ability even in samples with glucosuria.

[Semiquantitative glucose measurements in urine samples and urine soaked cat litter]. / Semiquantitative Glukosemessungen in Katzenharnproben und in mit Harn verklumpter Einstreu.

OBJECTIVE: Semiquantitative urine glucose measurements are a proposed alternative for the treatment surveillance of unmanageable diabetic cats. The primary objectives of this study were to determine the accuracy of 5 commercially available dipsticks, to re-evaluate a technique for detecting glucosuria in urine-soaked "clumping" type of cat litter described by Schaer and to validate a cat toilet with a sieve bottom. MATERIAL AND METHODS: A total of 93 urine samples were analysed using 5 different urine dipsticks. The correlation with a laboratory reference method and the diagnostic accuracy to diagnose pathological glucosuria > 1.48 mmol/l and urinary glucose concentrations ≥ 13.9 mmol/l (therapeutically important cut-off) were determined. Furthermore, the viability of 10 types of cat litter, a cat toilet with sieve bottom, 2 disinfectants, 2 cleaning agents and 2 cat litter deodorants were tested. RESULTS: The correlations of the dipstick results with the reference method were moderate (rSP = 0.633) to good (rSP = 0.846). The sensitivities and specificities to diagnose pathological glucosuria were 0.7-1 and 0.94-1, respectively. Urine glucose concentrations ≥ 13.9 mmol/l were detected with sensitivities of 0.65-1 and specificities of 0.97-1. Four cat litters, one dipstick and a disinfectant containing hydrogen peroxide caused false-positive colour reactions. Depending on the dipsticks and litter used, the measurements from soaked cat litter reduced the urine glucose concentrations by a median of 70-77 %. Pouring the probes into the cat toilet and subsequent measurements from the collecting tank did not falsify the results. CONCLUSION AND CLINICAL RELEVANCE: Not all urine dipsticks are suitable to monitor insulin therapy in diabetic cats. False positive colour reactions are possible when using dipsticks with high analytical sensitivities, some cat litters and oxidizing disinfectants. Measurements from the collecting tank of the cat toilet are superior to measurements using soaked clumping type of cat litter.

Evaluation of the effect of urine dip vs urine drip on multi-test strip results.

Standard operating procedures, including World Health Organization guidelines for packed cell volume, are established for in-clinic laboratory tests. No independent, evidence-based guidelines exist for dipstick urinalysis; however, manufacturer's instructions state to dip the stick into urine. In veterinary medicine, small volume urine samples could preclude dipping; therefore, a single drip per pad from a pipette or syringe is often performed. This study aimed to examine the differences between these two urine application methods prior to analysis, with the hypothesis that the method type would not effect on test results of dipstick analysis. To standardize the strip analysis method, a Siemens Clinitek Status + analyzer was used with Multistix10SG dipsticks. Three investigators tested urines from 53 dogs with a range of diseases by both methods. Results were assessed for the degree of agreement between the methods and within method variability. Overall, the agreement between methods was high. Within each method, the drip method variability was higher than that of the dip method (P = 0.012). Disagreements between methods were present, with pH and blood having the lowest agreement levels. Glucose was more likely to be positive on the drip compared with the dip methodology. This study demonstrates potential clinically relevant differences between the two methods and a higher level of variability with the drip methodology. Therefore, while the drip method could be used for practical reasons (eg, low sample volumes), this study supports the manufacturer's recommended method of dipping the dip stick into urine rather than dripping urine onto each pad with a pipette or syringe.

Effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor velagliflozin, a new drug with therapeutic potential to treat diabetes in cats.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are used in the treatment of human diabetics. They increase glucose excretion and correct hyperglycemia. We examined the investigational SGLT2 inhibitor velagliflozin in two groups of six neutered adult obese cats (equal gender distribution). Placebo (Pl) or drug (D; 1 mg/kg) was administered for 35 days. Routine blood examinations, fructosamine, beta-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucagon, adiponectin, and leptin were measured before and after treatment, also water intake, and urinary electrolytes, glucose, and volume. Indirect calorimetry, an intravenous glucose tolerance test (IVGTT; 0.8 g/kg) and insulin tolerance test (IVITT) were conducted. All cats tolerated treatment well. Significant changes with D included a decrease in the respiratory exchange ratio, an increase in cholesterol, a small increase in albumin, and a rise in BHB and NEFA. Glucose clearance was unaltered, although less insulin was secreted during the IVGTT (p = .056) suggesting improved insulin sensitivity. IVITT was unchanged. Treatment did not affect glucagon, leptin, or adiponectin. Water intake, urine output, urinary glucose excretion, and the glucose/creatinine ratio but not urinary electrolytes were significantly higher post-D. We conclude that velagliflozin is a promising drug, which increases urinary glucose excretion in cats and could thereby be beneficial for the treatment of hyperglycemia.

Transient renal Fanconi syndrome in a Chihuahua exposed to Chinese chicken jerky treats.

Transient Fanconi syndrome without azotemia was diagnosed in a dog and was associated with ingestion of Chinese chicken jerky treats. Fanconi syndrome is a proximal renal tubular defect and a diagnosis was made based upon severe glucosuria with normoglycemia, and severe generalized aminoaciduria. The clinical signs of polyuria and polydipsia as well as the massive urinary metabolic abnormalities resolved after jerky treat withdrawal. While frequently seen in North America and Australia, this is the first report of jerky treat induced Fanconi syndrome in continental Europe. Clinicians should be aware of this potential intoxication and be vigilant for a history of jerky treat consumption in a dog with glucosuria.

Long-term assessment of glucosuria in captive okapi (Okapia johnstoni) after a dietary change.

Glucosuria in okapis (Okapia johnstoni) was first documented in 1980, yet the etiology remains unclear. In August 2006, an attempt to lower glucosuria in captive okapi by diet modification (omitting all fruit and adding unmolassed beet pulp) was started at the Antwerp Zoo. To study the possible relationship between glucosuria and diet, stress, and/or pregnancy, four okapis were monitored over a period of 4.5 yr. One animal, born in 2006, became glucosuric near the age of three. Three okapis were adults at the start of the study and had been glucosuric for more than 5 yr. The glucose/creatinine urinary ratio values of these four glucosuric animals did not change considerably over time despite dietary changes. Stress did not appear to influence glucosuria in these okapi. Urinary ratio decreased during the second half of pregnancy in two females. In conclusion, the diet change did not reduce glucosuria, but pregnancy appeared to lower urinary glucose in okapis.

Analysis of glycosuria in okapi (Okapia johnstoni): examination of urinary N-acetyl-ß-D-glucosaminidase.

We analyzed the urinary excretion of glucose and N-acetyl-ß-D-glucosaminidase (NAG) in six okapis (Okapia johnstoni) in captivity to investigate the cause of their urinary sugar excretion. The urinary glucose-positive okapi had significantly higher urinary NAG indices than the urinary glucose-negative okapi. There was also a positive correlation between urinary glucose levels and urinary NAG indices. These results suggest that the proximal tubular function of the glycosuric okapi may have been obstructed, which impaired glucose reabsorption.

Association between urine osmolality and specific gravity in dogs and the effect of commonly measured urine solutes on that association.

OBJECTIVE: To determine the association between urine osmolality and specific gravity (USG) in dogs and to evaluate the effect of commonly measured urine solutes on that association. ANIMALS: 60 dogs evaluated by an internal medicine service. PROCEDURES: From each dog, urine was obtained by cystocentesis and USG was determined with a refractometer. The sample was divided, and one aliquot was sent to a diagnostic laboratory for urinalysis and the other was frozen at -80°C until osmolality was determined. Urine samples were thawed and osmolality was measured in duplicate with a freezing-point depression osmometer. The correlation between mean urine osmolality and USG was determined; the effect of pH, proteinuria, glucosuria, ketonuria, bilirubinuria, and hemoglobinuria on this relationship was investigated with multiple regression analysis. RESULTS: The Pearson correlation coefficient between urine osmolality and USG was 0.87. The final multivariable regression model for urine osmolality included USG and the presence of ketones; ketonuria had a small negative association with urine osmolality. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a strong linear correlation between osmolality and USG in urine samples obtained from dogs with various pathological conditions, and ketonuria had a small negative effect on that correlation.

Acquired proximal renal tubular dysfunction in 9 Labrador Retrievers with copper-associated hepatitis (2006-2012).

BACKGROUND: Copper-associated hepatitis (CAH) has been well described in Labrador Retrievers. However, the association of CAH with proximal renal tubular dysfunction in this breed has not been characterized. OBJECTIVES: To report clinical features, hepatic and renal histopathologic findings, tissue copper concentrations, and outcome of Labradors with CAH and proximal renal tubular disease. ANIMALS: Nine Labrador Retrievers with renal glucosuria and biopsy-confirmed CAH. METHODS: Clinical, clinicopathologic, and light microscopic findings were retrospectively reviewed. Rhodanine staining or atomic emission spectroscopy was performed on all hepatic samples and available renal tissue (4 dogs) to assess copper concentrations. RESULTS: Eight dogs had a history of polyuria and polydipsia, and all dogs had increased serum bilirubin concentrations. Five dogs had hyperchloremic metabolic acidosis. Three dogs with acidemia had paradoxical alkalinuria. All renal specimens had increased copper concentrations. Renal tubular vacuolization, degeneration, and regeneration were observed on light microscopy. Four dogs died within 10 days of diagnosis. One dog survived 2 months; 4 dogs survived more than 1 year. In long-term survivors, including 2 that did not undergo immediate copper chelation, resolution of renal tubular dysfunction occurred within weeks to months. CONCLUSIONS AND CLINICAL IMPORTANCE: Labrador Retrievers with CAH can develop clinical and laboratory evidence of renal tubular dysfunction in association with increased renal copper concentrations. Given the rarity of renal tubular disorders, detection of renal glucosuria and increased ALT activity in a Labrador Retriever is suggestive of CAH. Although renal tubular dysfunction may indicate advanced disease, successful long-term outcome is possible with a variety of therapies.

Glucosuria in Norwegian elkhounds and other breeds during dog shows.

Clinically healthy Norwegian elkhounds were tested for glucosuria by urine dipstick analysis and the results were compared with a group of dogs of other breeds during 15 dog shows. Fifty-two of 187 Norwegian elkhounds (27.3 per cent) and 15 of 202 dogs of other breeds (7.4 per cent) were glucosuric during the dog shows; the difference was statistically significant. Two of the glucosuric elkhounds and one non-glucosuric elkhound developed signs of kidney disease during the year of the study.

A pilot study comparing the diabetogenic effects of dexamethasone and prednisolone in cats.

Fourteen cats received either daily prednisolone (4.4 mg/kg per os [PO]) or dexamethasone (0.55 mg/kg PO) for 56 days. These doses were clinically equipotent. Serum fructosamine and urine glucose were measured on days 0, 28, and 56. Insulin sensitivity, glucose tolerance, and peak insulin secretion were measured in each group prior to and at the end of the courses of glucocorticoid administration. On day 56, the prevalence of glucosuria was significantly greater (P=0.027), and a trend was seen toward greater fructosamine concentrations (P=0.083) in dexamethasone-treated cats compared to prednisolone-treated cats. The results of this pilot study also showed a trend toward a greater decrease in insulin sensitivity (P=0.061) and a significantly lower compensatory increase in insulin secretion (P=0.081) in the dexamethasone-treated cats than in cats administered prednisolone. These preliminary data suggest that dexamethasone exhibits greater diabetogenic effects in cats than equipotent doses of prednisolone. Further study is justified to support this hypothesis.

Optimisation of the frequently sampled intravenous glucose tolerance test to reduce urinary glucose spilling in horses.

REASONS FOR PERFORMING STUDY: The frequently sampled i.v. glucose tolerance test (FSIGTT) is used to evaluate glucose and insulin dynamics in horses, but it has not been determined whether urinary glucose spilling (UGS) affects results. HYPOTHESIS: UGS occurs in horses during the FSIGTT and this problem can be minimised by adjusting the dextrose and insulin dosages used. METHODS: Six mature mares were included in this study. In the first phase, 6 FSIGTT procedures were performed in each horse to evaluate 6 different dextrose dosages. Six different insulin dosages were evaluated during the second phase of the study after administration of 300 mg/kg bwt dextrose. Area under the glucose (AUCg) and insulin (AUCi) curves were calculated and minimal model analyses performed. UGS was measured in the third and fourth phases of the study during the combined glucose insulin test and established FSIGTT. A new FSIGTT was developed and evaluated. RESULTS: Positive linear effects of dextrose dosage on AUCg, AUCi and acute insulin response to glucose were detected, with AUCg reaching a plateau at doses > or =200 mg/kg bwt. Insulin dosage had an inverse linear effect on AUCg, but other values remained unaffected. UGS occurred during all 3 tests and was the highest for the established FSIGTT and the lowest for the new FSIGTT. The type of FSIGTT performed did not affect minimal model results. CONCLUSIONS: Results indicate that the dextrose dosage of 300 mg/kg bwt used in the established FSIGTT is too high. UGS can be reduced by lowering the dextrose dosage to 100 mg/kg bwt. POTENTIAL RELEVANCE: A new FSIGTT involving the administration of 100 mg/kg bwt dextrose followed by 20 mu/kg bwt insulin 20 min later is recommended for use in horses because this test provides adequate data for minimal model analysis while minimising UGS.

Short communication: effect of temporary glycosuria on molasses consumption in Holstein calves.

This study was conducted to determine the effect of experimentally increased glucose demand on voluntary consumption of molasses by dairy calves. Three-week-old calves received 0.365 g of phlorizin by s.c. injection. Urinary output and molasses consumption were measured hourly, and urinary glucose concentration was screened. Molasses consumption for the 24 h after treatment was (mean +/- SE) 72.0 g (+/-7) for the control group and 142 g (+/-1) for the phlorizin-treated group. Urinary output for the 8-h test period was 1.13 kg for the control group and 1.67 kg for the phlorizin-treated calves. Mean urinary glucose peaked at 10 g/L by 4 h after treatment for calves given phlorizin, whereas the concentration for the control group remained close to 0 g/L. Phlorizin treatment increased voluntary consumption of molasses in 3-wk-old Holstein calves.

Evaluation the Clinitek status automated dipstick analysis device for semiquantitative testing of canine urine.

The aim of this prospective study was to evaluate the Clinitek status analyser using Multistix10SG/Microalbustix dipsticks (all: Siemens Dx) for canine urine (n=101) compared to reference methods: visual reading (Combur9 dipstick, Roche), refractometry, microscopy, and quantitative protein/creatinine analysis (Pentra400, AxonLab). The automated analyses were done twice and visual tests were performed by two examiners. An excellent to good concordance was demonstrated between the first/second analysis with the Multistix10SG and the Combur9 dipstick, respectively with Cohen's kappa-values ranging from 0.776 to 1.000. Agreement between both dipsticks was good for glucose (kappa=0.753), blood (kappa=0.793), protein (kappa=0.788), and moderate for bilirubin (kappa=0.431) and ketones (kappa=0.540). In 6/101 specimens, false positive ketone reactions were obtained with the Multistix10SG. Multistix10SG could not be used for determination of pyuria or specific gravity. Semiquantitative/quantitative protein results correlated well (rho=0.90) and creatinine measurements moderately (rho=0.76). Due to automated data transmission to the laboratory information system, the Clinitek status is of advantage in veterinary laboratories/clinics.

Metabolic adaptations associated with irreversible glucose loss are different to those observed during under-nutrition.

In this study the hypothesis that irreversible glucose loss results in an 'uncoupling' of the somatotrophic axis (increasing plasma GH levels and decreasing plasma IGF-I) was tested. During periods of negative energy balance the somatotrophic axis respond by increasing plasma GH and decreasing plasma IGF-I levels. In turn, elevated GH repartitions nutrient by increasing lipolysis and protein synthesis, and decreases protein degradation. Irreversible glucose loss was induced using sub-cutaneous injections of phloridizin. Seven non-lactating cows were treated with 8g/day phloridizin (PHZ) and seven control animals (CTRL, 0g/day), while being restricted to a diet of 80% maintenance. PHZ treatment increased urinary glucose excretion (P<0.001), resulting in hypoglycemia (P<0.001). As a response to this glucose loss, the PHZ treated animals had elevated plasma NEFA (P<0.005) and BHBA (P<0.001) levels. Average plasma insulin concentrations were not altered with PHZ treatment (P=0.059). Plasma GH was not different between the two groups (P>0.1), whereas plasma IGF-I levels decreased significantly (P<0.001) with PHZ treatment. The decline in plasma IGF-I concentrations was mirrored by a decrease in the abundance of hepatic IGF-I mRNA (P=0.005), in addition the abundance of hepatic mRNA for both growth hormone receptors (GHR(tot) and GHR(1A)) was also decreased (P<0.05). Therefore, the irreversible glucose loss resulted in a partial 'uncoupling' of the somatotrophic axis, as no increase in plasma GH levels occurred although plasma IGF-I levels, hepatic IGF-I mRNA declined, and the abundance of liver GH receptor mRNA declined.