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

Experimental diabetes alters intestinal mucosal function in a variety of ways including the enhancement of both active transport processes and the activity of brush-border hydrolases. These effects could result from changes in either intraluminal factors (food, bile, pancreatic enzymes) or extraluminal factors (blood flow, hormones, nervous impulses). To determine the role of intraluminal factors we studied the effect of diabetes on segments of jejunum completely excluded from luminal continuity, but with intact blood and nerve supply. Three weeks after construction of Thiry-Vella fistulas in rats, diabetes was induced with streptozotocin. Five days later sucrase activity was measured in both the excluded segment and in the proximal jejunum. Exclusion alone resulted in a 77 per cent decrease in mucosal protein content with no change in sucrase specific activity suggesting simply a diminished number of mucosal cells. Diabetes increased the specific activity of sucrase from 0.0643 mumoles per minute per milligram of protein plus or minus 0.0077 (SEM) to 0.1074 plus or minus 0.0182 (P smaller than 0.05) in the proximal jejunum and from 0.0467 plus or minus 0.0047 to 0.1040 plus or minus 0.0191 (P smaller than 0.02) in the excluded segment. These results provide conclusive evidence that the diabetic enhancement of sucrase activity is independent of intraluminal factors and must be the consequence of extraluminal changes.
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PMID:Enhancement of intestinal sucrase activity in experimental diabetes: the role of intraluminal factors. 12 49

The factors influencing the development of impaired sciatic motor nerve conduction velocity (MNCV) in acute experimental diabetes were examined. Decreased MNCV developed by the 14th day after streptozotocin administration but only in rats which became hyperglycemic. Insulin treatment, begun on day 3, failed to prevent imparied MNCV in diabetic rats in which improved or normal weight gain and a decreased degree of hyperglycemia was induced. However, insulin treatment prevented the development of impaired MNCV in a group of diabetic rats in which the tail vein plasma glucose concentration was never found to exceed 160 mg/dl during days 6 through 14, andin which the mean plus or minus SEM of the average plasma glucose concentration for each animal during the same period was 75 plus or minus 18 mg/dl. In normal rats fed diets containing 0.011% or 0.069% free myoinositol (a presumably normal range), sciatic nerve free myoinositol concentrations were 90- and 60-fold higher than those in plasma. On these diets the development of impaired MNCV in the diabetics was associated with a decrease in nerve free myoinositol as compared with nerves from normals fed the same diet, despite similar plasma levels in the normals and diabetics. Plasma and nerve free myoinositol increased with increasing dietary myoinositol content in both normals and diabetics, and nerve myoinositol content could be acutely increased by an i.p. myoinositol load. By supplementing the diets with 1.0% myoinositol, the difference in nerve myoinositol in normal and diabetic rats on day 14 was abolished; on this diet the development of impaired MNCV in the diabetics was moderated or totally prevented, despite persistent hyperglycemia and elevated nerve sorbitol and fructose concentrations. Insulin treatment that prevented impaired MNCV prevented a decrease in nerve myoinositol in diabetics. These studies suggest that insulin deficiency, and possibly hyperglycemia, are primary factors in the development of imparied MNCV in acute experimental diabetes. However, the development of impaired MNCV appears to be related in some manner to a derangement in the regulation of nerve free myoinositol content, which appears to be subject to modification by increases in plasma myoinositol concentration over a critical range.
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PMID:Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes. 12 20

Diabetes stimulates the functional activity of the intestinal brush border membrane with enhancement of both hydrolytic enzyme activity and membrane transport systems. To determine the mechanism of this effect, we studied the effects of streptozotocin diabetes on the metabolism of one membrane protein, sucrase-isomaltase, which increases its activity in diabetes. The protein was purified and an antiserum prepared. Sucrase-isomaltase from control and diabetic rats was immunologically identical as shown by Ouchterlony double-diffusion analysis of papain-solubilized mucosal proteins. The increase in sucrase enzyme activity in diabetic animals (31.0+/-1.4 U SEM 5 days after streptozotocin vs. 13.1+/-1.0 in controls) was the consequence of increased enzyme protein and not an alteration in catalytic efficiency as demonstrated by quantitative immunoprecipitin reactions. To account for increased sucrase-isomaltase protein in diabetes we studied papain-solubilized mucosal proteins labeled by injection of [(14)C]carbonate and [(14)C]leucine and analyzed incorporation into sucrase-isomaltase protein (anti-serum precipitable) and total protein (trichloroacetic acid precipitable). We found that diabetes did not affect the decay of labeled total protein, but prolonged the decay of labeled sucrase-isomaltase. t((1/2)) of sucrase-isomaltase was 4.4 h in control animals after [(14)C]carbonate injection and 8.8 and 10.2 h, respectively, 2 and 5 days after induction of streptozotocin diabetes. We obtained similar results in experiments with [(14)C]leucine with diabetes increasing t((1/2)) from 6 to 13.6 h. Diabetes did not appear to increase the rate of addition of sucrase-isomaltase to the brush border membrane, since it did not affect the 10- and 60-min incorporations of isotope into sucrase-isomaltase protein relative to incorporation into total protein and did not alter rate constants for synthesis calculated from the t((1/2)) and the change in enzyme mass over time.Thus, enhanced sucrase activity in the diabetic animal is the consequence of an increase in sucrase-isomaltase protein which develops because of a decrease in its rate of degradation.
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PMID:The intestinal brush border membrane in diabetes. Studies of sucrase-isomaltase metabolism in rats with streptozotocin diabetes. 14 62

The importance of the hepatic portal circulation in the response to insulin was assessed in streptozotocin-diabetic rats transplanted with syngeneic fetal pancreases. Partial reversal of diabetes was accomplished by transplantation of two or three fetal pancreases beneath the capsule of the kidney; complete reversal followed shunting of the venous drainage from the transplants to the liver. Plasma glucose after streptozotocin of 509+/-31 mg/dl (mean+/-SEM) fell after transplantation to 395+/-23 and after the shunt to 143+/-5 mg/dl. Urine volume fell from 84+/-4 to 50+/-5 ml/d and then to normal (17+/-1 ml/d) after the shunt. Glucose excretion which was 8.1+/-0.3 g/d after streptozotocin fell after transplantation to 4.8+/-0.3 g/d and after the shunt completely disappeared from the urine. The disappearance rate of glucose injected into the circulation, which was 0.50+/-0.07%/min in untreated diabetes, increased to 1.39+/-0.38%/min after transplantation and to 2.52+/-0.31%/min after the shunt, not different from normal controls (2.79+/-0.25). Plasma immunoreactive insulin (IRI) was below normal (25-35 muU/ml) and unresponsive to glucose in untreated diabetic rats. After transplantation IRI levels ranged from 73-223 muU/ml and there was no rise after glucose injection. After the shunt both the basal IRI (36+/-5 muU/ml) and the peak response to glucose at 10 min (58+/-7 muU/ml) were the same as in normal controls (42+/-4 and 62+/-7 muU/ml, respectively). The fall in IRI after the shunt is explained by increased extraction of insulin passing into the liver and also diminished secretion. After removal of the transplants plasma glucose and urine values returned almost to pretransplant levels. Secretion of insulin by transplanted pancreases into the liver enhances the effectiveness probably by increased extraction and action and reveals the importance of the normal route for insulin delivery.
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PMID:Importance of hepatic portal circulation for insulin action in streptozotocin-diabetic rats transplanted with fetal pancreases. 15 16

During the past decades insulin has been given in relatively high doses when treating diabetic coma. Recently low-dose insulin treatment has been proposed by several groups. In the reported investigation insulin was initially given in moderate to high doses (12-200 U/h) with a steady reduction in dose during the course of treatment. Insulin infusion was regulated either manually with an adjustable infusion pump (7 patients) or automatically with an artificial endocrine pancreas (glucose-controlled insulin infusion system; 11 patients). Thus 18 patients with decompensated diabetes mellitus (coma or precoma) were treated. In 14 patients with ketoacidotic decompensation laboratory data on hospital admission were: blood glucose 7.35 +/- 0.61 g/l, serum potassium 4.7 +/- 0.4 mmol/l, pH 7.1 +/- 0.04, base excess - 19,7 +/- 2.2 mmol/l (x +/- SEM). The other patients had hyperglycaemic or hyperosmolar non-ketotic decompensation. In all patients controlled reduction of blood glucose levels was achieved within 2.3 to 18 hours. The amounts of insulin infused during this ranged from 17 to 320 units, but in one instance was 1950 units. There were no complications.
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PMID:[Insulin treatment of decompensated diabetes mellitus with a new artificial endocrine pancreas (author's transl)]. 33 2

The studies so far reported on the metabolic clearance rate of insulin in human diabetes mellitus have given conflicting results, probably because they have been conducted on few patients and have used a variety of experimental techniques and data treatments. We investigated the kinetics of insulin distribution and degradation in 35 normal subjects and in 42 nonketotic, nonobese, overtly diabetic patients, of whom 26 were above 40 yr old and 16 were 40 yr old or less at diagnosis. The design of the study combined (a) the use of a tracer to perturb minimally the steady state and to avoid glucose infusion; (b) the preparation of purified [(125)I]-monoiodoinsulin, which has a metabolic behavior similar to that of native insulin; and (c) noncompartmental analysis of the plasma immunoprecipitable (125)I-insulin disappearance curves, which were recorded for 2 h after pulse i.v. injection of the tracer.Metabolic clearance rate was found to be similar in diabetics (404+/-18 ml/min.m(2), mean+/-SEM) and in normals (420+/-14), although the latter-onset patients had slightly, if not significantly, lower metabolic clearance rate values than the earlier-onset diabetics (385+/-19 and 443+/-36, respectively). The initial distribution volume of the hormone also did not significantly differ in diabetics and normals and was similar to plasma volume. The reentry rate into the initial distribution volume of the hormone and the total, plasma-equivalent distribution volume of insulin were both significantly raised in diabetics (251+/-12 ml/min.m(2) and 10.3+/-0.5 liters/m(2)) in comparison with normals (195+/-8 and 7.5+/-0.3). The posthepatic delivery rate of insulin was found to be slightly raised in later-onset diabetics (194+/-20 mU/h.m(2)), but somewhat reduced in earlier-onset diabetics (133+/-15) in comparison with normals (172+/-14); these differences reflected the different basal plasma insulin concentrations in these three groups. Chronic treatment with oral hypoglycemic drugs, age, duration of the disease, and degree of metabolic control appeared to have only little effect on the kinetics of insulin.On the basis of these results, we conclude that insulin-independent adult diabetics show, already in the fasting state, a combination of insulin resistance and insulin deficiency and a derangement in insulin distribution, the precise significance of which is uncertain.
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PMID:Kinetic analysis of plasma insulin disappearance in nonketotic diabetic patients and in normal subjects. A tracer study with 125I-insulin. 33 30

Pancreatic islet volumes of patients with and without maturity onset diabetes mellitus were estimated. The islet volume of the diabetic patients was 1.01 +/- 0.12 cm3 (SEM) and that of the non-diabetic patients 1.60 +/- 0.16 cm3 with considerable overlap between the two groups. Islet amyloidosis was found in all the diabetic and in 9 of the 15 non-diabetic patients. When the amyloid deposits were excluded, the islet volume of the diabetic patients was 0.89 +/- 0.10 cm3, while that of the non-diabetic patients was unchanged, 1.60 +/- 0.16 cm3. There was still some overlapping. Since amyloid deposits seem to destroy the B cell membranes, it was postulated that a comparison of the volumes of islets completely free of amyloid might give a more true picture of the quantitative islet alterations in maturity onset diabetes. It was found that this islet volume of the diabetics was only 0.41 +/- 0.05 cm3 and that of the non-diabetic patients 1.58 +/- 0.16 cm3. These values correspond better to the altered insulin secretion in maturity-onset diabetes mellitus.
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PMID:The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitus. 36 56

In 6 diabetic rats about 1,000 isolated islets of Langerhans were transplanted into the liver with little effect on the uninsulinism and hyperglycemia. Subsequently, a second transplantation resulted in a decrease of blood sugar to normal and in a reversal of the loss in body weight. Finally, in animals who had reversed to diabetes again, a third islet transplantation was performed. These rats with a total of 3,100 islets showed a decrease in the glucose levels from 250-305 to 110 +/- 27 (X +/- SEM) mg/100 ml. The insulin level after glucose stimulations was measured at 27 less than X less than 35 micromicron/ml.
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PMID:Multiple transplantation of islets of Langerhans. 41 20

Administration of dichloroacetate (DCA) to normal rats resulted in a fall in serum glucose and triglycerides and a rise in ketone bodies. Insulin and cholesterol levels were unchanged. The effects of DCA on lipid metabolism were examined in isolated rat hepatocytes. At 10 mM DCA, the incorporation of tritiated water into fatty acids (saponifiable lipids) was inhibited by 33 +/- 4% (mean +/- SEM, N = 5). No effect on incorporation into cholesterol (measured as nonsaponifiable lipids) was observed. DCA inhibited the incorporation of 14C-glucose into lipid but had no effect on glucose oxidation. Fatty acid oxidation was increased by 76 +/- 7% (mean +/- SEM, N = 6). However, DCA had no effect on the recovery of newly synthesized lipid. Thus, inhibition of tritiated water incorporation into fatty acids represents decreased synthesis rather than increased turnover. DCA did not affect the incorporation of 14C-palmitate into triglycerides or phospholipids. Cell viability, as assessed by incorporation of 3H-isoleucine into protein and trypan blue exclusion, was not affected by DCA. These results suggest that DCA lowers serum triglycerides through inhibition of fatty acid synthesis and stimulation of fatty acid oxidation by liver.
Diabetes 1979 Apr
PMID:Effects of dichloroacetate on lipid metabolism in isolated rat liver cells. 43 64

The effects of high-carbohydrate, high plant fiber (HCF) diets on glucose and lipid metabolism of 20 lean men receiving insulin therapy for diabetes mellitus were evaluated on a metabolic ward. All men received control diets for an average of 7 days followed by HCF diets for an average of 16 days. Diets were designed to be weight-maintaining and there were no significant alterations in body weight. The daily dose of insulin was lower for each patient on the HCF diet than on the control diet. The average insulin dose was reduced from 26 +/- 3 units/day (mean +/- SEM) on the control diets to 11 +/- 3 (P less than 0.001) on the HCF diets. On the HCF diets, insulin therapy could be discontinued in nine patients receiving 15 to 20 units/day and in two patients receiving 32 units/day. Fasting and 3-hr postprandial plasma glucose values were lower in most patients on the HCF diets than on the control diets despite lower insulin doses. Serum cholesterol values dropped from 206 +/- 10 mg/dl on the control diets to 147 +/- 5 (P less than 0.001) on the HCF diet; average fasting serum triglyceride values were not significantly altered on the HCF diets. These studies suggest that HCF diets may be the dietary therapy of choice for certain patients with the maturity-onset type of diabetes.
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PMID:High-carbohydrate, high-fiber diets for insulin-treated men with diabetes mellitus. 49 50


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