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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although it is agreed that autoimmune destruction of pancreatic islets in diabetic BB rats is rapid, reports of endocrine cell content of islets from BB diabetic rats at the time of onset of diabetes vary considerably. Because of the rapid onset of the disease (hours) and the attendant changes in islet morphology and insulin secretion, it was the aim of this study to compare islet beta-cell numbers to other islet endocrine cells as close to the time of onset of hyperglycemia as possible (within 12 h). As it has been reported that hyperglycemia renders the beta cell insensitive to glucose, the early effects of different levels of insulin therapy (well-controlled vs. poorly controlled glycemia) on islet morphology and insulin secretion were examined. When measured within 12 h of onset, insulin content of BB diabetic islets, measured by morphometric analysis or pancreatic extraction, was 60% of insulin content of control islets. Despite significant amounts of insulin remaining in the pancreas, 1-day diabetic rats exhibited fasting hyperglycemia and were glucose intolerant. The insulin response from the isolated perfused pancreas to glucose and the glucose-dependent insulinotropic hormone, gastric inhibitory polypeptide (GIP), was reduced by 95%. Islet content of other endocrine peptides, glucagon, somatostatin, and pancreatic polypeptide, was normal at onset and at 2 weeks post onset. A group of diabetic animals, maintained in a hyperglycemic state for 7 days with low doses of insulin, were compared with a group kept normoglycemic by appropriate insulin therapy. No insulin could be detected in islets of poorly controlled diabetics, while well-controlled animals had 30% of the normal islet insulin content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin secretion and islet endocrine cell content at onset and during the early stages of diabetes in the BB rat: effect of the level of glycemic control. 178 6

To examine the influence of coingestion of fat and protein in a mixed meal on carbohydrate metabolism, subjects with non-insulin-dependent diabetes mellitus (NIDDM) received three different breakfasts varying in the amount of fat and protein (group 1) or only in the amount of fat (group 2). Compared with the changes after a standard breakfast, insulin increased after the protein-rich meal and decreased after the fat-rich meal in group 1. Glucose and gastric inhibitory polypeptide (GIP) remained constant. In contrast, only GIP showed a significant increase after a high-fat meal in group 2. Thus, in NIDDM subjects, glucose and insulin responses to different mixed meals do not appear to be exclusively mediated by GIP. Protein was confirmed as a potent stimulator of insulin secretion. Other factors, such as an altered beta-cell response in diabetics to GIP or other incretions, must be considered to explain the reported results.
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PMID:Influence of breakfasts with different nutrient contents on glucose, C peptide, insulin, glucagon, triglycerides, and GIP in non-insulin-dependent diabetics. 198 41

We have studied the endocrine-metabolic status of patients in non-insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6-60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary blood glucose levels less than 7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute beta-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 May
PMID:Endocrine-metabolic function in remission-phase IDDM during administration of cyclosporine. 202 4

The effect of dietary sucrose and fat in the form of coconut fat (rich in saturated fatty acids) or safflowerseed oil (rich in polyunsaturated fatty acids) was examined on the development of obesity and impaired glucose homeostasis in ob/ob mice. Isoenergetic high sucrose or high fat diets were fed to ob/ob mice from 3-11 weeks of age. Energy intake of mice fed diets rich in fat were similar, and exceeded that attained with the sucrose diet. Body weight gain was greatest in the sucrose-fed mice and least in those fed safflowerseed oil. With the exception of insulin sensitivity which was enhanced with safflowerseed oil, plasma concentrations of glucose and gastric inhibitory polypeptide (GIP), glucose tolerance, intestinal GIP content and the GIP response to oral fat were similar. However, mice fed the high sucrose diet exhibited markedly elevated plasma insulin concentrations and an enhanced pancreatic insulin content. Since the hyperinsulinaemic action of sucrose cannot be attributed to elevated GIP or glucose concentrations, the involvement of other insulin-releasing hormones released from the intestine by sucrose is suggested. The results indicate that the relative amounts of carbohydrate and fat in the diet have an important modulating effect on the development of the ob/ob syndrome. The type of fatty acids in the diet does not appear to be a particularly important determinant for expression of the ob gene.
Diabetes Res 1990 Jan
PMID:Effects of diets rich in sucrose, coconut fat and safflowerseed oil on the development of the obese hyperglycaemic (ob/ob) syndrome in mice. 209 92

The pathophysiological role of incretin in diabetes mellitus has not been established. We therefore examined the effects of glucagonlike peptide I-(7-36)-amide (truncated GLP-I) and gastric inhibitory polypeptide (GIP) on insulin and glucagon release from isolated perfused pancreases of diabetic rats (12-14 wk of age, mean +/- SE fasting plasma glucose 8.9 +/- 0.6 mM, n = 25) after an injection of 90 mg/kg streptozocin on the 2nd day after birth and compared the results with those of nondiabetic control rats. In diabetic rats, the infusion of 1 nM GLP-I or GIP in perfusates with varying glucose concentrations (2.8, 5.6, 8.3, 11.1, or 22.2 mM) caused a nearly equal degree of insulin stimulation from a similar basal insulin level. Meanwhile, basal and GLP-I- or GIP-stimulated insulin release increased in correlation with the ambient glucose concentration in nondiabetic rats. The degree of stimulation of insulin release at glucose concentrations of 5.6 mM in diabetic rats was approximately 33% that of nondiabetic rats. The stimulation potency was the same between GLP-I and GIP. The insulin treatment for diabetic rats (5 U/kg NPH insulin at 0900 and 2100 for 6 days) brought only a slight improvement in the glucose dependency of GLP-I-stimulated insulin release. The effects of GLP-I and GIP on glucagon release were completely opposite. GLP-I suppressed release; GIP stimulated it. In diabetic rats, the degree of suppression by GLP-I and stimulation by GIP were almost the same with similar basal glucagon levels in the perfusate with varying glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Nov
PMID:Reduced insulinotropic effects of glucagonlike peptide I-(7-36)-amide and gastric inhibitory polypeptide in isolated perfused diabetic rat pancreas. 214 78

Modifying the rate of absorption has been proposed as a therapeutic principle of specific relevance to diabetes. To demonstrate clearly the metabolic benefits that might result from reducing the rate of nutrient delivery, nine healthy volunteers took 50 g glucose in 700 ml water on two occasions: over 5-10 min (bolus) and at a constant rate over 3.5 h (sipping). Despite similar 4-h blood glucose areas, large reductions were seen in serum insulin (54 +/- 10%, P less than 0.001) and C-peptide (47 +/- 12%, P less than 0.01) areas after sipping, together with lower gastric inhibitory polypeptide and enteroglucagon levels and urinary catecholamine output. There was also prolonged suppression of plasma glucagon, growth hormone, and free-fatty acid (FFA) levels after sipping, whereas these levels rose 3-4 h after the glucose bolus. An intravenous glucose tolerance test at 4 h demonstrated a 48 +/- 10% (P less than 0.01) more rapid decline in blood glucose (Kg) after sipping than after the bolus. Furthermore, FFA and total branched-chain amino acid levels as additional markers of insulin action were lower over this period despite similar absolute levels of insulin and C-peptide. These findings indicate that prolonging the rate of glucose absorption enhances insulin economy and glucose disposal.
Diabetes 1990 Jul
PMID:Metabolic effects of reducing rate of glucose ingestion by single bolus versus continuous sipping. 219 84

Mechanisms by which various classes of extracellular signals regulate insulin secretion are discussed regarding their cellular and molecular actions. Under physiological circumstances, the small postprandial changes in plasma glucose concentrations (approximately 4.4-6.6 mM) primarily serve as a conditioned modifier of insulin secretion and dramatically alter the responsiveness of islets to a combination of neurohormonal agonists. These agonists have two functions. Cholecystokinin (CCK) and acetylcholine activate the hydrolysis of polyphosphoinositides, and gastric inhibitory polypeptide (GIP) and glucagonlike peptide 1 activate adenylate cyclase. These two functional classes of neurohumoral agonists act synergistically to enhance insulin secretion when plasma glucose is greater than 6.0 mM but not when it is less than or equal to 4 mM. On the other hand, an increase in plasma glucose concentration to 8-10 mM induces an increase in insulin secretory rate in the absence of any of the neurohormonal agonists. Remarkably, high glucose leads to an increase in the same intracellular signals, as does a combination of acetylcholine and GIP. On the basis of these data, a model of how insulin secretion is regulated under physiological circumstances is proposed. This model emphasizes that the regulation of insulin secretion occurs in three stages: cephalic, early enteric, and later enteric. In this view, the crucial event occurring during the first two phases is the agonist-induced, translocation of protein kinase C (PKC) to the plasma membrane under conditions in which an increase in Ca2+ influx does not occur. PKC is now in a cellular location and a Ca2(+)-sensitive conformation such that an increase in Ca2+ influx rate occurring during the third phase leads to its immediate activation and an enhanced rate of insulin secretion. Furthermore, under physiological circumstances, an optimal insulin secretory response is dependent on a correct temporal pattern of signals arising from neural and enteric sources. If this pattern is deranged, an abnormal pattern of insulin secretion is observed. An important new insight is provided by the observation that agonists (e.g., CCK or acetylcholine) that act to stimulate the hydrolysis of phosphatidylinositides, when acting for a short period (10-20 min), induce an enhanced responsiveness of islets to glucose, i.e., proemial sensitization. However, when acting unopposed for several hours, these agonists will induce a time-dependent suppression of responsiveness to glucose and other agonists. The latter observation implies that optimal insulin secretion is dependent on periodic rather than a continuous exposure to the correct pattern of extracellular signals.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes Care 1990 Jun
PMID:Physiology and pathophysiology of insulin secretion. 219 49

In previous studies we found that in healthy subjects, 5 and 10 g of a partially purified amylase inhibitor delayed and decreased starch digestion and reduced postprandial plasma glucose after a starch meal but produced diarrhea in two of six and four of six subjects, respectively. Thus, we wondered whether lower doses of the inhibitor, when given with a meal that contained protein and fat as well as carbohydrate, would have the same effect on carbohydrate tolerance without causing diarrhea. Eight healthy subjects were randomized to receive 2.0 or 2.9 g of the inhibitor with a 650-calorie meal that contained carbohydrate, fat, and protein. In comparison with a placebo, ingestion of 2.9 g, but not 2.0 g, of the inhibitor significantly reduced postprandial increases in plasma glucose (P less than 0.05), C peptide (P less than 0.03), and gastric inhibitory polypeptide (P less than 0.008). Similarly, 2.9 g of the inhibitor in comparison with 2.0 g was associated with more carbohydrate malabsorption and more breath hydrogen excretion. Because the carbohydrate malabsorption observed with the 2.9-g dose was similar to that with the previously tested 5- and 10-g doses of the inhibitor but diarrhea was less frequent, impurities in the partially purified preparation may, in part, have been responsible for these adverse effects. We conclude that 2.9 g of the amylase inhibitor given with a meal that contains a mixture of nutrients is effective in increasing carbohydrate tolerance without causing diarrhea. Therefore, this dose is appropriate for use in studies to determine whether the inhibitor has a beneficial effect in patients with diabetes mellitus or obesity.
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PMID:Effect of a purified amylase inhibitor on carbohydrate metabolism after a mixed meal in healthy humans. 243 11

Rye flakes, rye bread and white wheat bread were given as suspensions to rats and in standardized breakfast meals to non-insulin-dependent diabetics. In both cases the postprandial glucose response was lower after rye bread than after wheat bread. A larger amount of starch remained in the stomach of the rats 15 min after ingesting rye bread compared to wheat bread, indicating that delayed gastric emptying may be one factor explaining the lower response after rye bread. Although the incremental postprandial glucose areas after rye flakes and wheat bread were similar, the rate of decrease of the glucose curve was slower after flaked rye. This would point to a prolonged absorption of some starch in the rye flakes, also indicated by higher late immunoreactive insulin (IRI) values after that product. In the rats the content of starch in the stomachs 15 min after feeding was higher after rye flakes compared to wheat bread. In vitro incubations with alpha-amylase showed lower availability of the starch in rye flakes than in the breads, indicating that several factors may contribute to the differential postprandial glucose response after the wheat and rye products. The levels of insulin, C-peptide, gastric inhibitory polypeptide (GIP), glucagon, somatostatin, triglyceride and glycerol were followed after the breakfast meals. No pronounced differences of these parameters were seen. However, wheat bread gave significantly higher glucagon and GIP responses than did rye flakes. In conclusion, the absorption pattern and metabolic response after rye bread seems preferable to that after wheat bread. The flaked rye on the other hand was not effective in reducing postprandial glycaemia despite a lower availability of starch in vitro.
Diabetes Res Clin Pract
PMID:Rye products in the diabetic diet. Postprandial glucose and hormonal responses in non-insulin-dependent diabetic patients as compared to starch availability in vitro and experiments in rats. 243 70

A partially purified amylase inhibitor given with a single meal causes maldigestion of carbohydrate, increases delivery of carbohydrate to the ileum, and reduces postprandial plasma glucose. To determine the effect of more prolonged administration of the inhibitor on gastrointestinal function and carbohydrate tolerance, we studied 6 non-insulin-dependent diabetics (3 previously treated with oral agents and 3 treated with diet alone) for 3 wk while they ate a weight-maintenance diet. Patients taking oral agents continued them during the first week. During the second week, 4-6 g of the inhibitor was given with each meal. Capillary blood glucose concentration was measured before each meal and 90 min postprandially. On the last day of each week venous blood samples for glucose, hormones, and lactic acid analysis and a quantitative stool culture were obtained. Total carbohydrate absorption was estimated by comparing postprandial breath hydrogen on study days 7, 14, and 21 with breath hydrogen after ingesting 15 g of lactulose on days 0, 15, and 22. There 24-h stools were collected and weighed at the end of each week and analyzed for carbohydrate, lactic acid, short-chain fatty acids, pH, dry matter, amylase, and fat. The inhibitor significantly (p less than 0.05) reduced postprandial plasma glucose, C-peptide, insulin, and gastric inhibitory polypeptide concentrations, significantly increased (p less than 0.05) breath hydrogen excretion, and caused carbohydrate malabsorption. Diarrhea occurred the first day the inhibitor was ingested, but thereafter cessation of diarrhea was associated with changes in the metabolism of carbohydrate by colonic flora. As the amylase inhibitor improves carbohydrate homeostasis and is not associated with continuing diarrhea, it may be a useful adjuvant in the treatment of patients with non-insulin-dependent diabetes mellitus.
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PMID:Gastrointestinal and metabolic effects of amylase inhibition in diabetics. 244 48


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