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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperglycaemia may enhance insulin resistance typical of non-insulin dependent diabetes mellitus, as well as insulin dependent diabetes mellitus, and thus initiate a vicious pathogenetic cycle. We sought to test the hypothesis that reduction in chronic hyperglycaemia in the diabetic dog by methods that do not employ insulin may improve insulin resistance. We used the glucuretic agent phlorizin in dogs rendered chronically hyperglycaemic and diabetic by alloxan treatment. To analyse glucose disposition the euglycaemic clamp was performed. To minimize the role of counterregulatory influences that might be at play when glucose is reduced, the hyperglycaemic clamp with continuous somatostatin infusion was performed. Although phlorizin normalised plasma glucose in the diabetic dog and reduced plasma glucose in normal, non-diabetic dogs, insulin dependent glucose disposition rate did not improve. While phlorizin itself was associated with insulin resistance in the normal animals, the insulin resistance of diabetes mellitus was not further augmented. We conclude that phlorizin is associated with insulin resistance perhaps by a common pathway shared by chronic hyperglycaemia. Care must be taken when phlorizin is used as an agent to study glucose disposition.
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PMID:Antecedent chronic hyperglycaemia blocks phlorizin-induced insulin resistance in the dog. 338 20

Vascular smooth muscle contractile responses to neuropeptide Y, alpha,beta-methyleneATP and noradrenaline were studied in circular segments of isolated vessels with intact endothelium in vitro from 12 patients with diabetes mellitus type 2 (NIDDM) and 12 control subjects. The dilatory effect of acetylcholine was used to test the function of the endothelium. Subcutaneous arteries and veins (diameter 0.1-1.1 mm) were obtained during surgery. There was no difference in contractile responses to noradrenaline or alpha,beta-methyleneATP between diabetic and control vessels. The contractile response to neuropeptide Y, however, was markedly reduced in the diabetic group. The maximal contractile effect (46.0 +/- 14.0%, p < 0.05) but not the sensitivity to neuropeptide Y was significantly less in diabetic veins compared to control (107.5 +/- 19.6%). Thus, the attenuation of neuropeptide Y responses was present in humans as previously observed in alloxan-induced diabetes mellitus in rabbits. There was no difference in the dilator effect of acetylcholine between the diabetic and the control group in any of the vessel types, indicating that the difference in vascular reactivity to neuropeptide Y was not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of neuropeptide Y, a co-transmitter of the peripheral sympathetic nervous system, is selectively attenuated in diabetes mellitus.
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PMID:Selective attenuation of neuropeptide-Y-mediated contractile responses in blood vessels from patients with diabetes mellitus. 852 Feb 13

This study was undertaken to investigate D-400, a herbomineral formulation in streptozotocin induced diabetes in rats. Glycated haemoglobin, lipid profile and glucose tolerance test were studied. D-400 has an established hypoglycaemic effect in alloxan induced diabetes in rats as well as in non-insulin dependent diabetes mellitus patients. D-400 treated group showed lower glycated haemoglobin, triglycerides and higher HDL levels. The hyperglycaemic response was blunted after administration of oral glucose in the same group.
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PMID:Effect of D-400, a herbomineral preparation on lipid profile, glycated haemoglobin and glucose tolerance in streptozotocin induced diabetes in rats. 857 14

Biguanides are used for the treatment of non-insulin dependent diabetes mellitus but there is no evidence for an improving action of biguanide on the enhancement of peripheral glucose disposal in type 1 diabetes. It is known that biguanide agents reduce the oxidation of free fatty acids. Using alloxan and streptozotocin (STZ) induced diabetic rats as a model for type 1 diabetes mellitus, we measured insulin binding capacity and plasma lipid peroxidation levels before and after metformin induction. There was a significant increase in insulin binding capacity and lipid peroxidation levels in alloxan and STZ diabetes compared to controls. We examined the effect of metformin on alloxan and STZ-induced diabetic rats. In alloxan-induced diabetes metformin (Met) treatment led to an increase in insulin receptor number in liver plasma membranes (before Met: 46.50 +/- 2.69, after Met: 76.00 +/- 3.39 fmol/mg, p < 0.001) and a decrease in plasma lipid peroxidation levels compared to the non-treated group (before Met: 1.85 +/- 0.53, after Met: 1.10 +/- 0.09 nmol MDA/ml, p < 0.05). In STZ-induced diabetic rats metformin treatment did not change the lipid peroxidation levels (before Met: 1.26 +/- 0.31, after Met: 1.38 +/- 0.44 nmol MDA/ml, p > 0.05) whereas it did increase the receptor numbers (before Met: 41.60 +/- 4.33, after Met: 63.40 +/- 8.64 fmol/mg, p < 0.002).
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PMID:The effect of metformin on insulin receptors and lipid peroxidation in alloxan and streptozotocin induced diabetes. 885 72

Effects of taurine supplementation on lipid peroxide formation and the activities of glutathione (GSH) dependent enzymes in diabetic model mice were investigated. Type I diabetes mellitus was induced by injecting alloxan to ICR mice while type II diabetes mellitus was produced by high calorie diet feeding to genetically hyperglycemic KK mice. Taurine was given in drinking water at the level of 5% (w/v) for seven days. The malondialdehyde (MDA) levels of liver and the islets of type I diabetes were significantly increased compared to the control group but the levels were significantly decreased by taurine supplementation. In the type II diabetic model, the concentrations of MDA were not changed by taurine treatment. The activity of hepatic and islet GSH-peroxidase (GPX) was increased in the type I diabetic group, but in type II animals it was decreased. Hepatic GPX activity of both type I and II diabetics was not altered by taurine supplementation but was increased in the islets of the type II animals. No effect on the activity of GSH S-transferase (GST) was observed in both types of diabetes (I and II) following taurine supplementation. These results suggest that taurine supplementation protects type I diabetic mice from lipid peroxide formation.
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PMID:Effect of taurine supplementation on the lipid peroxide formation and the activities of glutathione-related enzymes in the liver and islet of type I and II diabetic model mice. 963 20

Several studies have shown that the activities of delta-6-desaturase and delta-5-desaturase are depressed in experimental diabetes and in humans with insulin- and non-insulin-dependent diabetes mellitus (type I and type II diabetes mellitus respectively). Furthermore, treatment with insulin is known to correct the defects in desaturases in rats and humans with diabetes, especially in type I. In a recent study, we demonstrated that L-arginine and nitric oxide can prevent alloxan-induced beta cell damage, and the severity of diabetes, and restore the antioxidant status to near normal levels. But, no information is available as to the relationship between L-arginine-nitric oxide system and the metabolism of essential fatty acids in diabetes mellitus. In the present study, it was noted that the plasma levels of saturated fatty acids: stearic and palmitic were increased where as unsaturated fatty acids such as oleic, linoleic, gamma-linolenic and eicosapentaenoic acids (OA, LA, GLA and EPA respectively) were decreased in alloxan-induced diabetic rats. In the liver phospholipid (PL) fraction, GLA, DGLA (dihomo-GLA) and alpha-linolenic acid (ALA) were decreased in the alloxan-treated group; in the muscle PL fraction, LA, GLA and DGLA were low, whereas an increase in the saturated fatty acid content was noted. L-arginine (the precursor of nitric oxide) and sodium nitroprusside (a nitric oxide donor) treatment of alloxan-induced diabetic rats enhanced the levels of LA, GLA and DGLA. Further, nitric oxide synthase inhibitor, L-NMMA, prevented this beneficial action of L-arginine-nitric oxide system on essential fatty acid metabolism. The abnormalities in the essential fatty acid metabolism observed also reverted to normalcy following control of diabetes with insulin. These results indicate that nitric oxide can enhance the activities of delta-6- and delta-5 desaturases, which are depressed in diabetes, and suggests that there is a close interaction between L-arginine-nitric oxide system and the metabolism of essential fatty acids.
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PMID:Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus. 1076 77

JTT-501, a new insulin sensitizer, improves peripheral glucose uptake in insulin-resistant animals such as KK-Ay mice and Zucker fatty rats. However, the effect of JTT-501 on hepatic glucose metabolism has not been addressed. To investigate this effect, experiments were performed on 6 alloxan-diabetic dogs. Three experiments were conducted for each dog: the treatment experiment, which followed a 10-day oral treatment with JTT-501 30 mg x kg(-1) x d(-1), and 2 control experiments 2 weeks before and 2 weeks after the treatment experiment. A hyperinsulinemic-hyperglycemic clamp was performed with the tracer dilution method (intraportal insulin infusion rate, 18 pmol x kg(-1) x min(-1)). Arterial hyperglycemia (approximately 10 mmol/L) was maintained by adjusting the peripheral glucose infusion rate. After a 45-minute basal period (period I), portal glucose infusion (22.2 micromol x kg(-1)min(-1)) was administered for 120 minutes (period II). This was followed by a 90-minutes recovery period (period III). JTT-501 increased insulin-stimulated glucose utilization (P < .05) and enhanced insulin-mediated suppression of glucose production (P < .05) in periods I and III. Net hepatic glucose balance (NHGB) determined by the arterial-venous (A-V) difference method was increased by JTT-501 in period II (P < .01). We conclude that JTT-501 enhances both hepatic and peripheral insulin sensitivity and therefore may have important therapeutic effects in type 2 diabetes.
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PMID:Effect of JTT-501 on net hepatic glucose balance and peripheral glucose uptake in alloxan-induced diabetic dogs. 1090 96

Most insulin is secreted in discrete pulses at an interval of approximately 6 min. Increased insulin secretion after meal ingestion is achieved through the mechanism of amplification of the burst mass. Conversely, in type 2 diabetes, insulin secretion is impaired as a consequence of decreased insulin pulse mass. beta-cell mass is reported to be deficient in type 2 diabetes. We tested the hypothesis that decreased beta-cell mass leads to decreased insulin pulse mass. Insulin secretion was examined before and after an approximately 60% decrease in beta-cell mass achieved by a single injection of alloxan in a porcine model. Alloxan injection resulted in stable diabetes (fasting plasma glucose 7.4 +/- 1.1 vs. 4.4 +/- 0.1 mmol/l; P < 0.01) with impaired insulin secretion in the fasting and fed states and during a hyperglycemic clamp (decreased by 54, 80, and 90%, respectively). Deconvolution analysis revealed a selective decrease in insulin pulse mass (by 54, 60, and 90%) with no change in pulse frequency. Rhythm analysis revealed no change in the periodicity of regular oscillations after alloxan administration in the fasting state but was unable to detect stable rhythms reliably after enteric or intravenous glucose stimulation. After alloxan administration, insulin secretion and insulin pulse mass (but not insulin pulse interval) decreased in relation to beta-cell mass. However, the decreased pulse mass (and pulse amplitude delivered to the liver) was associated with a decrease in hepatic insulin clearance, which partially offset the decreased insulin secretion. Despite hyperglycemia, postprandial glucagon concentrations were increased after alloxan administration (103.4 +/- 6.3 vs. 92.2 +/- 2.5 pg/ml; P < 0.01). We conclude that an alloxan-induced selective decrease in beta-cell mass leads to deficient insulin secretion by attenuating insulin pulse mass, and that the latter is associated with decreased hepatic insulin clearance and relative hyperglucagonemia, thereby emulating the pattern of islet dysfunction observed in type 2 diabetes.
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PMID:Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced postprandial hepatic insulin clearance, and relative hyperglucagonemia in the minipig. 1152 65

Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disease resulting primarily from a variety of pancreatic beta-cell disorders and insulin resistance. Whereas insulin resistance, which constitutes a defect in insulin action, increases the risk of developing NIDDM and, as such, is a predictor of the onset of this disease, it is mostly the beta-cell dysfunction in regulating insulin secretion which yields the chronic hyperglycemia with all its associated clinical complications. The individual steps in the secretory pathway of insulin which is induced primarily by blood plasma glucose have now been identified. The transport of the sugar into the beta-cell is followed by its phosphorylation as the rate-determining step. The glycolytic metabolism of glucose-6-phosphate leads to the generation of ATP resulting in increases in beta-cell ATP pools (steady-state-levels) as well as ATP/ADP ratios, which, in turn, produce the closure of ATP-sensitive K(+) channels, thus depolarizing the beta-cell membrane and opening of Ca(2+) channels. The resulting influx of extracellular Ca(2+) and the increase in recruitment of Ca(2+) from intracellular stores in response to extracellular signals yield an increase in total [Ca(2+)](i) which activates the granular insulin secretory machinery. The intracellular beta-cell ATP pools have a key role in transducing the signals of the stimulus-secretion coupling pathway and toxins such as alloxan and streptozotocin which produce experimental diabetes in animals act by damaging mitochondrial oxidative phosphorylation, leading to permanent decreases in cellular ATP pools which, due to the sensitivity of beta-cell function to these pools, manifest itself as a form of diabetes. In addition to the major effects of blood plasma glucose in the regulation of insulin secretion, a variety of hormonal and neural factors producing endocrine and paracrine effects modulate and fine-tune beta-cell insulin secretion. The enteroinsular axis provides a linkage between the gastrointestinal tract and pancreatic beta-cells stimulus-secretion pathway. Although a powerful effect of ATP on insulin secretion was demonstrated more than 30 years ago, only recently has it been shown that beta-cells possess P(2)-purinoceptors. Extracellular ATP and its synthetic agonists are insulin secretagogues by virtue of their activation of membrane purinergic receptors which is coupled to increases in extracellular Ca(2+) influx and mobilization of Ca(2+) from internal stores resulting in insulin release from beta-cell granules. The physiological significance of extracellular ATP regulation of insulin secretion as well as the physiological source of these ATP pools have not yet been established. It has been recently demonstrated that the administration of adenine nucleotides in vivo can yield significant increases in tissue, blood (red blood cell), and blood plasma ATP pools. Increasing pancreatic beta-cell intracellular and blood plasma (extracellular) pools of ATP is a new therapeutic modality in non-insulin-dependent diabetes mellitus.
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PMID:Involvement of Elevated Intracellular and Extracellular ATP in the Regulation of Insulin Secretion: Therapeutic Targets in Non-Insulin-Dependent Diabetes Mellitus. 1185 Jun 64

The effect of oropharyngeal administration of insulin lente (BP, USP) on alloxan-induced diabetic rabbits was investigated. In mild cases of hyperglycaemia (below 500 mg/dl), a buccal dose of 100 IU was able to produce significant reduction in blood glucose levels over seven hours, as compared with diabetic animals during the same period. As much as 60% reduction in glucose level from the starting level could be achieved. However, at very high levels of hyperglycaemia (above 500 mg/dl), this regimen failed to produce normoglycaemia although it rendered the animal tolerant to high levels of glucose. This mode of administration of insulin did not produce hypoglycaemia in any of the animals: the blood levels in the mildly diabetic animals were reduced to normoglycaemia without progressing into the hypoglycaemic state. The administration of insulin to normoglycaemic rabbits by this route did not produce any reduction in glucose levels. This preliminary report suggests that a noninvasive oropharyngeal route may be an alternative for the clinical management of insulin and non-insulin dependent diabetes mellitus in man.
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PMID:Effects of oropharyngeal/buccal insulin on glucose levels in alloxan-induced diabetic rabbits: clinical implications. 1215 61


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