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Query: UMLS:C0011849 (diabetes)
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Disturbances of gastrointestinal motility are a common feature of diabetes mellitus and are usually ascribed to autonomic neuropathy. In order to assess the role of other factors on changes in motility in diabetes we have studied the stomach to caecum transit time (SCTT) during the progression of streptozotocin induced diabetes in the rat. Rats were used one, two, four, and eight weeks after a single injection of streptozotocin and age matched animals were used as controls. In further experiments non-diabetic rats received a bolus injection of pancreatic glucagon (50 or 75 micrograms intraperitoneally) or its diluent. SCTT was estimated using the non-invasive hydrogen excretion method. SCTT was unaffected by the age of the animal (mean (SEM) value: 101 (5) min), but was significantly delayed at one week (139 (11) min, p less than 0.01), two weeks (163 (16) min, p less than 0.01), four weeks (148 (9) min, p less than 0.01), and eight weeks (171 (13) min, p less than 0.01) after streptozotocin. SCTT was also slower during hyperglucagonaemia (control 96 (6) min; glucagon treated 50 micrograms: 120 (7) min, p less than 0.05 and 75 micrograms: 127 (8), p less than 0.05). Since autonomic neuropathy is not a recognised feature of the initial stages of diabetes hyperglucagonaemia may be responsible, at least in part, for diabetes induced changes in gastrointestinal motility.
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PMID:Delayed stomach to caecum transit time in the diabetic rat. Possible role of hyperglucagonaemia. 237 69

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

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

Spontaneous diabetes in the non-obese diabetic (NOD) mice is a CD4 T cell-dependent process. We have suggested that specific beta cell destruction results from free radical production at the site of islet inflammation; oxygen radicals are produced by activated inflammatory cells. We reported here that in vivo treatment of spontaneously diabetic NOD mice with the enzyme superoxide dismutase (2000 U for seven injections) and catalase (40,000 U for seven injections) protects islet tissue from disease recurrence following transplantation into spontaneously diabetic mice. Similar results were obtained when animals were treated with either enzyme alone. This effect was dose-dependent and little protection was observed when the dose of enzyme was reduced four-fold. These results indicate that oxygen metabolites, specially superoxide and hydrogen peroxide, are directly involved in the pathogenesis of immunology mediated diabetes.
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PMID:Involvement of O2 radicals in 'autoimmune' diabetes. 254 56

Recent studies indicate that hydrogen-labeled glucose tracers underestimate glucose turnover in humans under conditions of high flux. The cause of this underestimation is unknown. To determine whether the error is time-, pool-, model-, or insulin-dependent, glucose turnover was measured simultaneously with [6-3H]-, [6,6-2H2]-, and [6-14C]glucose during a 7-h infusion of either insulin (1 mU.kg-1.min-1) or saline. During the insulin infusion, steady-state glucose turnover measured with both [6-3H]glucose (8.0 +/- 0.5 mg.kg-1.min-1) and [6,6-2H2]glucose (7.6 +/- 0.5 mg.kg-1.min-1) was lower (P less than .01) than either the glucose infusion rate required to maintain euglycemia (9.8 +/- 0.7 mg.kg-1.min-1) or glucose turnover determined with [6-14C]glucose and corrected for Cori cycle activity (9.8 +/- 0.7 mg.kg-1.min-1). Consequently "negative" glucose production rates (P less than .01) were obtained with either [6-3H]- or [6,6-2H2]- but not [6-14C]glucose. The difference between turnover estimated with [6-3H]glucose and actual glucose disposal (or 14C glucose flux) did not decrease with time and was not dependent on duration of isotope infusion. During saline infusion, estimates of glucose turnover were similar regardless of the glucose tracer used. High-performance liquid chromatography of the radioactive glucose tracer and plasma revealed the presence of a tritiated nonglucose contaminant. Although the contaminant represented only 1.5% of the radioactivity in the [6-3H]glucose infusate, its clearance was 10-fold less (P less than .001) than that of [6-3H]glucose. This resulted in accumulation in plasma, with the contaminant accounting for 16.6 +/- 2.09 and 10.8 +/- 0.9% of what customarily is assumed to be plasma glucose radioactivity during the insulin or saline infusion, respectively (P less than .01). When corrected for the presence of the contaminant, glucose turnover determined with [6-3H]glucose during insulin infusion (9.5 +/- 0.6 mg.kg-1.min-1) no longer differed from either the glucose infusion rate or that determined with [6-14C]glucose. Therefore, the underestimation of glucose turnover during insulin infusion and negative glucose production rates observed with traditional methods to analyze plasma radioactivity and commercially available tracers is the result of an artifactual increase in [6-3H]glucose specific activity. The etiology of the underestimation of glucose turnover with [6,6-2H2]glucose remains to be determined.
Diabetes 1989 Jan
PMID:Underestimation of glucose turnover measured with [6-3H]- and [6,6-2H]- but not [6-14C]glucose during hyperinsulinemia in humans. 264 38

Studies have shown that glycation in vitro is complicated by the ability of glucose to oxidise, in the presence of trace amounts of transition metal, generating protein-reactive ketoaldehydes, hydrogen peroxide and diverse free radicals. Protein exposed to glucose undergoes fragmentational and conformational alterations, and these, as well as thiol oxidation, appear to be caused by hydroxyl radicals. Glycofluorophore formation is dependent upon ketoaldehyde formation. It is suggested that glucose autoxidation contributes to oxidative stress in pathophysiology associated with diabetes and ageing via this newly described process of "autoxidative glycosylation".
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PMID:"Autoxidative glycosylation": free radicals and glycation theory. 267 32

The application of in vivo MR spectroscopy to the study of the liver is currently an expanding field of research. Owing to technical difficulties, the results obtained thus far were mainly those of animal observations. Several nuclei have been considered: hydrogen, phosphorus, carbon or fluorine. This non-traumatic method allows following and quantifying the various metabolic pathways, especially during hepatic diseases. The major metabolic pathways, i.e. neoglycogenesis, glycogenolysis, Krebs' cycle, etc., are studied, as well as their alterations during diseases such as ischemia, diabetes or alcoholism. The development of this promising technique requires the cooperation of various clinical and fundamental disciplines.
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PMID:[In vivo NMR spectroscopy of the liver]. 267 30

The studied group comprised 47 women in the 3rd trimester of pregnancy (29-40 weeks), including 17 with type I diabetes (study group) and 30 healthy women (control group). In the study group in one case diabetes was diagnosed during pregnancy and treated with diet only, in the remaining 16 pregnant women the mean diabetes duration was 6.2 years and the mean daily insulin dose was 70 u. According to White's classification one patient was in class A, 10 in class B and 6 in class C. In all cases renal function was normal, with normal blood values of creatinine, urea, electrolytes, uric acid, protein and acid-base equilibrium. Endogenous creatinine clearance was also normal. The studied biochemical parameters of renal tubular function included: 1) deamination of amino acids--with measurement of ammonium ion (NH4+) excretion with urine, 2) carbonic acid metabolism--with determination of urinary excretion of hydrogen ions (H+), 3) urinary excretion of sodium (Na+) and potassium (K+) ions. Besides that 24-hour urine was always measured. The studied women were similarly hydrated (standard diet, fluid balance control). The results were subjected to statistical analysis. In women with type I diabetes the volume of 24-hour urine was increased, although it fell within the normal range, urinary excretion of Na+ and K+ was raised. No change was found in amino-acid deamination an carbonic acid metabolism since the excretion of NH4+ and H+ was normal.
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PMID:[Various biochemical parameters of renal tubular function in patients with type I diabetes in the third trimester of pregnancy]. 270 87

To investigate diabetic alterations of small intestinal transit and bacterial growth, we performed hydrogen breath tests (10 g lactulose via duodenal tube at the ligament of Treitz), bacterial cultures, and determinations of unconjugated serum bile acids in 19 patients with long-standing diabetes and 7 healthy controls. Asymptomatic diabetics had a late rise in breath hydrogen, indicating prolonged jejunal-cecal transit (86 +/- 10 min, p less than 0.05) as an early pathogenic event. Rise in breath hydrogen in symptomatic diabetics (constipation: 50 +/- 6 min; diarrhea: 41 +/- 11 min) was not significantly different from controls (57 +/- 8 min). Bacterial studies and increased unconjugated serum bile acids suggest bacterial overgrowth in some symptomatic diabetics. Bacterial overgrowth was associated more frequently (p less than 0.05) with a rise in breath hydrogen before 45 min or after 75 min. Changes in the hydrogen breath test, bacterial growth, or unconjugated serum bile acids did not correlate with gastrointestinal symptoms of diabetes.
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PMID:Small intestinal transit, bacterial growth, and bowel habits in diabetes mellitus. 271 3

We have examined polyol pathway kinetics in the lenses of rats made diabetic with streptozotocin. At up to 11 days after diabetes induction, the lenses were isolated and subjected to 'pulse-chase' studies: the lenses were incubated with [13C]glucose and lens metabolism followed by [13C]nuclear magnetic resonance (NMR) spectroscopy. Proton NMR spectroscopy was also performed to measure the hexose monophosphate shunt (HMPS) activity. The results showed that (1) the activity of aldose reductase increased initially and decreased after 11 days of diabetes; (2) the fructose pool increased initially but started to decline after 3 days; (3) the HMPS activity increased nearly 40% immediately after diabetes induction; and (4) the turnover rates of glucose, alpha-glycerophosphate (GP), lactate, sorbitol, and fructose were 80.8 +/- 2.6, 10.1 +/- 1.4, 47.7 +/- 3.7, 7.9 +/- 0.9 and 5.2 +/- 2.2 nmol hr-1 lens-1 (34 mg wet weight lens-1), respectively. Up to 35% of lactate appeared to derive from the polyol pathway. Further, GP was rapidly metabolized, although its fate is currently unknown. These results reveal a far more complex pattern of glucose metabolism in the diabetic lens than that in lenses incubated in high glucose.
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PMID:Polyol pathway activity in streptozotocin-diabetic rat lens. 275 93


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