Effect of dose and modification of viscous properties of oat gum on plasma glucose and insulin following an oral glucose load.

An extract from oats known as oat gum (OG) is composed mainly of the polysaccharide (1-->3) (1-->4)-beta-D-glucan, which is highly viscous in aqueous solution. Viscous polysaccharides are known to attenuate postprandial plasma glucose and insulin responses. The purposes of this study were to determine the dose-response to OG and establish quantitatively the effect of viscosity on plasma glucose and insulin levels of healthy humans consuming 50 g glucose. Increasing the dose of OG successively reduced the plasma glucose and insulin responses relative to a control without gum. Reduction of the viscosity of OG by acid hydrolysis reduced or eliminated the capacity to decrease postprandial glucose and insulin levels. The ability of OG to modify glycaemic response was unchanged following agglomeration in the presence of maltodextrin. Agglomerated gum dispersed smoothly in a drink without formation of lumps, and development of maximum viscosity was delayed. These properties improve palatability. There was a highly significant linear relationship between log[viscosity] of the mixtures consumed and the glucose and insulin responses. The relationship shows that 79-96% of the changes in plasma glucose and insulin are attributable to viscosity, and that changes occur at relatively low doses and viscosities.

Oat beta-glucan reduces blood cholesterol concentration in hypercholesterolemic subjects.

OBJECTIVE: Several studies have indicated that consumption of oat bran lowers blood cholesterol and this effect has been attributed specifically to oat bran's soluble fiber (beta-glucan). This study was designed to test this hypothesis. DESIGN: The purified fibre (oat gum, 80% beta-glucan) was isolated, and agglomerated in the presence of maltodextrin to facilitate dispersion in a drink. Subjects consumed the oat gum (2.9 g beta-glucan), or maltodextrin placebo, twice daily for 4 weeks, in a randomized, cross-over design with a 3 week wash-out between phases. Consumption was equivalent to a daily dose of about 70 g of oat bran. SETTING: The study was with free-living individuals. SUBJECTS: Twenty hypercholesterolemic male and female adults entered, and 19 completed, the study. INTERVENTIONS: Blood lipids from fasting individuals were measured weekly throughout the study. Diet was monitored using 3 day food diaries. RESULTS: There were no significant changes (P > 0.05) in blood lipids during the placebo phase. Mean initial total cholesterol (6.76 +/- 0.13 mmol/l) and low density lipoprotein (LDL) cholesterol (4.59 +/- 0.14 mmol/l) levels fell throughout the oat gum phase, and at week 4 each was reduced 9% relative to initial values (P = 0.0004 and 0.005 respectively). When oat gum was discontinued, total and LDL cholesterol returned to initial levels. There were no significant changes in high density lipoprotein (HDL) cholesterol. Triglyceride levels also remained unchanged except for a singular decrease at week 4 of the oat gum phase relative to the initial value, but not compared to the placebo value. The lowered mean total and LDL cholesterol levels occurred in the absence of any dietary changes. CONCLUSIONS: The main component of the soluble fibre of oats, beta-glucan, significantly reduced the total and LDL cholesterol levels of hypercholesterolemic adults without changing HDL cholesterol.

High beta-glucan oat bran and oat gum reduce postprandial blood glucose and insulin in subjects with and without type 2 diabetes.

The aim of the current study was to characterize the effects of isolated and native sources of beta-glucan, oat gum, and oat bran, respectively, when incorporated into a complete meal. Fasting control subjects and subjects with Type 2 diabetes were fed porridge meals containing either wheat farina, wheat farina plus oat gum or oat bran. Blood samples were collected for 3 h after the test meals and plasma glucose and insulin were measured. Oat bran and wheat farina plus oat gum meals reduced the postprandial plasma glucose excursions and insulin levels when compared with the control wheat farina meal in both control and Type 2 diabetic subjects. This study shows that both the native cell wall fibre of oat bran and isolated oat gum, when incorporated into a meal, act similarly by lowering postprandial plasma glucose and insulin levels. A diet rich in beta-glucan may therefore be of benefit in the regulation of postprandial plasma glucose levels in subjects with Type 2 diabetes.

Oat gum lowers glucose and insulin after an oral glucose load.

Foods containing soluble dietary fibers delay glucose absorption and lower postprandial plasma glucose. This effect of oat bran has been attributed to oat gum (80% beta-glucan). However, purified oat gum has previously not been available for human studies. In this study the glucose and insulin responses to consuming 14.5 g of specifically prepared oat gum with 50 g glucose were compared with the response to guar gum with glucose and to glucose alone in nine healthy, fasting subjects. Plasma glucose and insulin increases after the glucose drink were greater than after both gum meals between 20 and 60 min (P less than 0.01). The responses to the two gum meals were nearly identical. These results establish that the more palatable oat gum lowers postprandial plasma glucose and insulin concentrations in humans and may be comparable with or of greater benefit than guar gum.

Long-term culture of neonatal rat pancreatic endocrine cells as model for insulin-secretion and ion-channel studies.

So far, only freshly isolated cells or short-term cultures have been used to study ion-channel activity in pancreatic nontumor beta-cells. We report a procedure for the long-term cultivation of pancreatic endocrine cells to study the relationship between ion channels and insulin secretion. Using thimerosal to suppress fibroblastoid cell proliferation and a preliminary 2-day cell exposure to alternating normal (5.6 mM) and high (16.7 mM) glucose levels, we observed a significant secretory responsiveness of the cells to a glucose challenge for at least 4 wk in culture. Cells also responded to glucose or other secretagogues, such as quinine and the sulfonylurea glyburide, with membrane voltage oscillations. In the cell-attached configuration of the patch-clamp technique, a 65-pS-conductance K+ channel was observed, which was inhibited by glucose, quinine, and glyburide. In the inside-out configuration, the activity of this channel was suppressed by ATP applied to the cytoplasmic side of the membrane. A K+ channel with a conductance of 200 pS was also observed, which was activated by intracellular Ca2+. A 13-pS-conductance glucose-insensitive K+ channel was present in both cell-attached and inside-out patch recordings. Even after 3 wk, the characteristics of these currents and channels were comparable to those reported by other investigators with freshly dissociated or short-term-cultured beta-cells from neonatal and adult rats and adult mice. Therefore, the neonatal rat endocrine cell culture characterized herein provides an improved model for long-term investigations combining secretion and electrophysiological studies.

Hyperosmolar nonketotic diabetic coma: diagnosis and management.

Hyperosmolar nonketotic diabetic coma (HHNC) is a syndrome of acute decompensation of diabetes mellitus, occurring mainly in the elderly and characterized by marked hyperglycemia, hyperosmolarity, severe dehydration, occasional neurological signs, obtunded sensorium, and absence of ketonemia or acidosis. The mortality is high. Early aggressive therapy with large amounts of normal or half normal saline, insulin, and potassium is of prime importance. Since associated diseases cause most fatalities the importance of managing these problems effectively cannot be overemphasized. Complications of therapy can be congestive heart failure secondary to excessive fluid administration, hypoglycemia if too much insulin is given, and hypokalemia if potassium is inadequately replaced.

Ketone body kinetics in humans: the effects of insulin-dependent diabetes, obesity, and starvation.

The kinetics of acetoacetate (A) and beta-hydroxybutyrate (B) have been studied following the injection as a pulse or continued infusion of [3-14C]acetoacetate (A*) or [14C]beta-hydroxybutyrate (B*) into six newly diagnosed, untreated, ketotic diabetic patients, ten obese subjects in the postabsorptive state, and the ten obese subjects after 1-2 weeks starvation (50 cal per day). Employing a compartmental model of acetoacetate and beta-hydroxybutyrate kinetics developed using CONSAM for normal subjects, the rate coefficients (Lij), rates of release of newly synthesized acetoacetate and beta-hydroxybutyrate into the blood (UA, UB), and fractional removal of each compound (FCRA and FCRB) were calculated. Ketone body release into blood (UA + UB) in diabetic subjects was threefold higher than normal (mean +/- SD, 208 +/- 118 versus 81 +/- 66 mumol min-1 m-2) and in obese subjects the rate increased on starvation from 171 +/- 70 to 569 +/- 286 mumol min-1 m-2. In each case most of the increase was in beta-hydroxybutyrate. The major change in diabetes and on starvation of the obese subjects was in the rate coefficient for removal of ketone bodies. Normally 0.168 +/- 0.109 min-1, it was 0.055 +/- 0.040 min-1 in the diabetic patients and fell from 0.066 +/- 0.040 to 0.027 +/- 0.019 min-1 in the obese subjects on starvation. In normal subjects, FCRA was similar to FCRB (0.226 +/- 0.142 versus 0.188 +/- 0.124 min-1). However, in diabetics, FCRA was 0.074 +/- 0.044 and FCRB was 0.050 +/- 0.034 min-1 and both were lower than normal. On starvation of obese subjects, FCRA fell from 0.199 +/- 0.047 to 0.089 +/- 0.035 min-1, whereas FCRB fell from 0.141 +/- 0.040 to 0.033 +/- 0.012 min-1. Therefore, the removal of beta-hydroxybutyrate was impaired more than that of acetoacetate in all patients. Our results confirm previous observations that ketosis is associated with high rates of ketogenesis and a decrease in fractional clearance. In addition, we found that in diabetes, obesity, and in obese subjects following starvation, most of the increased synthesis was in beta-hydroxybutyrate and that the clearance of beta-hydroxybutyrate decreased more than that of acetoacetate.

Time course of serum glucoregulatory variables and lipids following neonatal thymectomy of diabetes-prone and control BB Wistar rats fed a defined diet.

The acute diabetic syndrome in the BB Wistar rat resembles human type 1 (insulin-dependent) diabetes, including a possible association with T cell-mediated, (auto)immune processes. In most previous studies 'normoglycemic' littermates of diabetic BB rats have been used as controls and little attention has been paid to the role of diet. It now appears that asymptomatic/diabetes-prone littermates of diabetics have immune system defects as well as metabolic abnormalities. Since there are also indicators that the disease process starts before animals become symptomatic, we looked for prospective metabolic changes in prediabetic, asymptomatic/diabetes-prone and control (diabetes-free) BB rats following intervention in the immune system while maintaining the animals on a defined diet (AIN-76). The results reported here confirm and extend the finding of Like et al. (1982) that neonatal thymectomy reduces the frequency of the syndrome and emphasize the role of diet in modifying its expression. In contrast to previous reports of hyperglucagonemia only after onset of diabetes, asymptomatic/diabetes-prone animals had periodic increases of plasma glucagon values up to 3-fold those of diabetes-free controls; prediabetics displayed a similar pattern. Asymptomatic/diabetes-prone rats also tended to have slightly higher blood cholesterol levels. The low incidence and delayed onset of the syndrome in rats fed a modified AIN-76 diet (27%, 127 +/- 21 days) compared to the previous chow-fed generation (60%, 93 +/- 18 days) and chow-fed littermates (38%, 87 +/- 16 days) suggested that diet can modify expression of the syndrome.

Diabetic ketoacidosis during long-term treatment with continuous subcutaneous insulin infusion.

During 1880 patient-months of treatment with continuous subcutaneous insulin infusion in 101 patients with IDDM, 36 episodes of acute, severe loss of glycemic control, including 29 with significant ketoacidosis, occurred in 20 patients. Fifteen episodes were attributable to failure of insulin delivery to the patient while 13 were precipitated by infection. Insufficiently frequent blood glucose monitoring, failure by patients to detect mechanical and technical problems with infusion systems, failure to adhere to "sick day" regimens, and delay in seeking medical help all contributed to the progression of a number of episodes. Thirst, nausea, and vomiting were the common clinical manifestations of decompensation; and the degree of acidemia was often mild in relation to the degree of hyperglycemia. Response to conventional management was usually prompt.

Gastrin in the perinatal rat pancreas and gastric antrum: immunofluorescence localization of pancreatic gastrin cells and gastrin secretion in monolayer cell cultures.

The presence and development of immunoreactive gastrin (IRGa) in the fetal and neonatal pancreas and pyloric antrum of the rat were studied. IRGa appeared in both organs at least as early as the 16th day of fetal life. Antral IRGa increased rapidly and continuously in the neonatal period, while pancreatic IRGa concentration increased and was maintained at a relatively constant level from days 5 to 35. Monolayer cell cultures of the neonatal rat pancreas were used to evaluate the role of cyclic AMP mediated release of gastrin. The addition of N6,O2'-dibutyryl cyclic AMP (4 mM) or theophylline (4 mM) to the culture medium induced significant release of gastrin. The stimulation of adenylate cyclase with cholera toxin (10 ng/ml) also resulted in significant gastrin release. Long-term cultures (18-24 days) were shown to release gastrin continuously at a relatively constant rate. The cellular localization of pancreatic gastrin in 7-day-old cultures was performed by immunological techniques, using fluorescein-labeled antibodies to gastrin. The gastrin-containing cells were located at the periphery of most of the endocrine cell clusters. Immunofluorescence techniques for insulin and glucagon also showed that the alpha cells had a similar peripheral distribution, although they were more frequent in number. In contrast, insulin-containing cells were numerous and were present in all areas of the endocrine cell clusters. The studies support the following conclusions: a) Gastrin is present in the rat pancreas, even as early as late fetal life; b) Gastrin-producing cells are present and functionally competent in monolayer cell cultures of the neonatal rat pancreas for prolonged periods of time (24 days); c) Gastrin is released from these cells when intracellular levels of cyclic AMP are increased; d) By immunofluorescence methods, the gastrin-producing cells in pancreatic cell cultures are found to be located at the periphery of the endocrine cell clusters.

Purification of monolayer cell cultures of the endocrine pancreas.

Experimental use of primary cultures of endocrine pancreas is constrained by early, vigorous proliferation of fibroblastoid cells. The addition of heavy metals, sodium ethylmercurithiosalicylate, phenyl mercuric acetate, phenyl mercuric nitrate and sodium aurothiomalate to the culture media selectively destroys these fibroblastoid cells yielding highly enriched, morphologically intact, functionally competent endocrine cells that are capable of cell replication. This action of heavy metals appears to be due to reversible inhibition of sulfhydryl enzymes since glutathione and thioglycolate were demonstrated to completely inhibit the cytotoxic effects of the mercury and gold containing agents, respectively. Certain variables in the application of the mercurial agents to pancreatic endocrine cell cultures were defined, most notably the enhanced sensitivity of fetal vs. neonatal tissue, and in inverse relationship of cell density to effective toxicity. After removal of the heavy metal agent from the culture media, many pancreatic islets send out cytoplasmic projections, containing large numbers of oriented microtubules which serve as bridging units to adjacent endocrine cells. The sustained availability of virtually pure pancreatic endocrine cell cultures, which results from the application of mercury to the culture media will undoubtedly permit many aspects of the cell biology of the endocrine pancreas to be directly and sequentially assailed.

The effect of insulin on the alpha-cell response to hyperglycemia in long-standing alloxan diabetes.

In acute experimental diabetes in animals, alpha-cell unresponsiveness to hyperglycemia can be promptly corrected by insulin, but in human diabetes, even massive doses of insulin have little effect. To determine if this inability of insulin to correct the alpha-cell abnormality in man is merely the consequence of the long duration of the diabetic state (rather than of a difference in mechanism), the effect of insulin was studied in alloxan diabetes of long duration. Alloxan-diabetic dogs were maintained for 7-18 mo and treated daily with insulin. When glucose was infused without insulin, glucagon did not decline but rose paradoxically. However, when insulin was infused at a rate of 9 mU/kg/min together with glucose, a prompt decline in glucagon from a base-line average of 171 pg/ml SEM+/-34 to a nadir of 41 pg/ml SEM+/-9 was observed. This decline indicated that alpha-cell responsiveness to hyperglycemia is completely restored by large quantities of insulin. To determine if small amounts of insulin would similarly restore alpha-cell responsiveness in long-standing experimental diabetes, 1.4 mU/kg/min was infused. By the time the mean insulin level had risen 43 muU/ml, glucagon had declined significantly and ultimately fell to a nadir of 44 pg/ml. It is concluded from these studies that alpha-cell responsiveness to hyperglycemia can be fully restored in long-standing alloxandiabetic dogs as readily as in acutely diabetic dogs. Its ineffectiveness in restoring alpha-cell responsiveness to hyperglycemia in human diabetes may not, therefore, be related to duration of the diabetic state, and may reflect a primary alpha-cell defect.