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

To study the role of pancreatic beta-cell function in glucose intolerance and frank diabetes that sometimes develops in cirrhosis, the C-peptide response to a bolus IV injection of 1 mg of glucagon was measured in nine controls and in two groups of patients with cirrhosis. The first group comprised nine subjects with normal or high-normal fasting plasma glucose and no glycosuria; five of them had impaired glucose tolerance. The second group consisted of eight cirrhotics in whom frank diabetes had developed six to 48 months after the diagnosis of cirrhosis. They were characterized by fasting plasma glucose greater than 140 mg/dL and permanent glycosuria. No differences in the degree of liver impairment or portal-systemic shunting were observed between the two groups. Plasma glucose response to glucagon was similarly reduced in cirrhotic subjects. Basal C-peptide was high normal in patients with cirrhosis, and significantly increased in nondiabetic subjects. By contrast peak C-peptide levels and total C-peptide responses to glucagon were low normal in cirrhotics and significantly reduced in patients with cirrhosis and diabetes. In 14 patients the C-peptide response to a standard meal was also measured. It was significantly reduced in patients with cirrhosis and diabetes (six cases), as compared to cirrhotic subjects without diabetes. Peak C-peptide after IV glucagon significantly correlated with peak C-peptide after the meal (r = .927), or total C-peptide response to meal (r = .871). Impaired insulin secretion may add to insulin resistance in patients with liver cirrhosis, leading to the development of frank diabetes, characterized by fasting hyperglycemia and glycosuria.
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PMID:Pancreatic beta-cell function in cirrhotic patients with and without overt diabetes. C-peptide response to glucagon and to meal. 389 76

The mechanisms contributing to the impairment in glucose metabolism in non-insulin-dependent diabetes mellitus, insulin-dependent diabetes mellitus, and diabetic ketoacidosis are summarized in Table 2. Impaired insulin secretion is characteristic of patients with IDD and DKA. In contrast, insulin secretion in NIDD may be normal, increased, or decreased. Peripheral tissue resistance to the action of insulin is present in all three diabetic conditions; it is moderate in NIDD and IDD and severe in DKA. Basal hepatic glucose production in NIDD and IDD can be either normal or increased, and correlates closely with the fasting plasma glucose concentration. In DKA, HGP is elevated. Suppression of HGP by insulin is normal in NIDD and IDD but severely impaired in DKA. Hepatic glucose uptake following oral glucose is decreased in NIDD; hepatic uptake of ingested glucose has not been examined in IDD and DKA.
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PMID:Insulin resistance: a universal finding in diabetic states. 682 Sep 36

Impaired insulin secretion occurs at some stage in the development of non-insulin-dependent diabetes mellitus (NIDDM), possibly during impaired glucose tolerance (IGT) or early NIDDM. To assess insulin secretion at these critical stages, we measured the first-phase insulin response (to glucose and arginine), maximal secretory capacity, and glucose potentiation slope for insulin secretion in Pima Indians with normal glucose tolerance (n = 20), IGT (n = 9), and mild (fasting glucose < 7.8 mmol/L) NIDDM (n = 7). We also measured oral glucose tolerance and insulin action. Subjects with IGT were more insulin-resistant (P < .05) than normals. A wide range of insulin secretion was noted, although as a group, no significant impairment was detected. Subjects with mild NIDDM were similarly insulin-resistant, but they also had impaired insulin secretion. The first-phase response to glucose was markedly reduced in absolute terms (P < .001), but all secretion indices were impaired relative to the degree of insulin resistance (P = .05 to P < .0001). These results suggest that in Pima Indians, impairment of insulin secretion, especially the first-phase response to glucose, is associated with mild NIDDM. Insulin secretion in IGT is variable and, overall, seems intact, although a subtle defect in the first-phase insulin response to glucose could not be ruled out in this study. Glucose sensing for first-phase secretion may be one of the early secretory defects in the progression of glucose intolerance and seems to be critical at the transition from IGT to early NIDDM.
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PMID:In vivo beta-cell function at the transition to early non-insulin-dependent diabetes mellitus. 778 60

Impaired insulin secretion and/or insulin resistance are the primary defect(s) in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Both seem to be regulated by the genetic factors in addition to environmental factors. Recent Advances are revealing the molecular mechanism how insulin is secreted in response to glucose and how insulin acts on the target tissues. Several genes including glucokinase and mitochondria have been shown to be responsible for the development of NIDDM, but NIDDM is the polygenic disease and most of NIDDM patients may have still-uncharacterized diabetogenic factors.
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PMID:[Heterogeneity in pathogenesis of NIDDM and recent advances in research of diabetogenic genes]. 798 98

Impaired insulin secretion is a characteristic of non-insulin-dependent diabetes mellitus (NIDDM). One possible therapeutic agent for NIDDM is the insulinotropic hormone glucagon-like peptide 1 (GLP-1). GLP-1 stimulates insulin secretion through several mechanisms including activation of protein kinase A (PKA). We now demonstrate that the subcellular targeting of PKA through association with A-kinase-anchoring proteins (AKAPs) facilitates GLP-1-mediated insulin secretion. Disruption of PKA anchoring by the introduction of anchoring inhibitor peptides or expression of soluble AKAP fragments blocks GLP-1 action in primary islets and cAMP-responsive insulin secretion in clonal beta cells (RINm5F). Displacement of PKA also prevented cAMP-mediated elevation of intracellular calcium suggesting that localized PKA phosphorylation events augment calcium flux.
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PMID:Anchoring of protein kinase A facilitates hormone-mediated insulin secretion. 940 18

Impaired insulin secretion is a hallmark in both type I and type II diabetic individuals. Whereas type I (insulin-dependent diabetes mellitus) implies ss-cell destruction, type II (non-insulin dependent diabetes mellitus), responsible for 75% of diabetic syndromes, involves diminished glucose-dependent secretion of insulin from pancreatic beta-cells. Although a clear demonstration of a direct effect of 17beta-estradiol on the pancreatic ss-cell is lacking, an in vivo insulinotropic effect has been suggested. In this report we describe the effects of 17beta-estradiol in mouse pancreatic ss-cells. 17beta-Estradiol, at physiological concentrations, closes K(ATP) channels, which are also targets for antidiabetic sulfonylureas, in a rapid and reversible manner. Furthermore, in synergy with glucose, 17beta-estradiol depolarizes the plasma membrane, eliciting electrical activity and intracellular calcium signals, which in turn enhance insulin secretion. These effects occur through a receptor located at the plasma membrane, distinct from the classic cytosolic estrogen receptor. Specific competitive binding and localization of 17beta-estradiol receptors at the plasma membrane was demonstrated using confocal reflective microscopy and immunocytochemistry. Gaining deeper knowledge of the effect induced by 17beta-estradiol may be important in order to better understand the hormonal regulation of insulin secretion and for the treatment of NIDDM. receptor.
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PMID:Rapid insulinotropic effect of 17beta-estradiol via a plasma membrane receptor. 976 77

Non-insulin dependent diabetes mellitus (NIDDM) has a substantial genetic component. Impaired insulin secretion, insulin insensitivity in muscle and adipose tissue, and elevated hepatic glucose production are the major pathophysiological features of NIDDM. Insulin insensitivity is also a feature of the insulin resistance syndrome, which describes the epidemiological association of glucose intolerance, upper body obesity, hyperinsulinaemia, hypertension, increased triglyceride levels and decreased high-density-lipoprotein (HDL)-cholesterol concentrations. Insulin insensitivity has been found to be a familial trait, and this raises the hypothesis that the insulin resistance syndrome may also occur as a familial trait in caucasian families in association with the development of NIDDM. The 90 first degree relatives of 50 caucasian subjects with NIDDM were studied with a continuous infusion glucose tolerance test to quantitate glucose tolerance, insulin sensitivity and beta-cell function. Body mass index (BMI), blood pressure, fasting triglyceride and HDL-cholesterol measurements were obtained, and the intercorrelations between these variables were examined. As a group the first degree relatives had a median insulin sensitivity of 65% (interquartile range 46-99%). Insulin sensitivity was univariately correlated with systolic and diastolic blood pressure, triglyceride and HDL-cholesterol. These associations were present in both the hyperglycaemic and the normoglycaemic relatives. The hyperglycaemic relatives were significantly more insulin insensitive than the normoglycaemic relatives, but this additional insulin insensitivity was not associated with significant differences in blood pressure, triglyceride or HDL-cholesterol concentrations. Our data indicate that the insulin insensitivity present in the first degree relatives of subjects with NIDDM is correlated with the cardiovascular risk factors which make up the insulin resistance syndrome, and that glycaemic status does not appear to be the major determinant of these associations. Interventions targeting obesity and insulin insensitivity in these subjects may reduce cardiovascular risk.
Diabetes Res Clin Pract 1998 Nov
PMID:The relationship between the insulin resistance syndrome and insulin sensitivity in the first-degree relatives of subjects with non-insulin dependent diabetes mellitus. 988 45

The metabolic characteristics of type 2 diabetes, insulin resistance, and diminished insulin secretion are costly to measure directly. To evaluate the utility of several simple indices derived from insulin and glucose measurements, the indices were examined from 1982 to 1997 with respect to correlation with more sophisticated measures of insulin sensitivity and secretion in Pima Indians in the Gila River Indian Community of Arizona. Ability to predict the incidence of diabetes in 1,731 persons was also examined. Indices were calculated from fasting and 2-hour glucose (G0, G120) and insulin (I0, I120) concentrations obtained during an oral glucose tolerance test. Fasting serum insulin concentration and the insulin sensitivity index (10(4)/(I0 x G0)) each showed a moderate correlation with the estimate of insulin sensitivity derived from the hyperinsulinemic-euglycemic clamp (absolute value r approximately 0.60). They also strongly predicted the incidence of diabetes (incidence rate ratio comparing the most and least insulin-resistant tertile groups approximately 3.0). Corrected insulin response (I120/(G120 x (G120 - 70))) was modestly correlated with insulin secretion as measured by an intravenous glucose tolerance test (r = 0.35). Impaired insulin secretion assessed by this index predicted incidence of diabetes, particularly after control for insulin sensitivity index (incidence rate ratio = 1.6). Thus, simple indices of insulin sensitivity and secretion may be reasonable surrogates for more sophisticated measures in epidemiologic studies.
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PMID:Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. 1064 22

Impaired insulin secretion and insulin resistance are thought to be two major causes of type 2 diabetes mellitus. There are two kinds of diabetic model mice: one is a K(ATP) channel knockout (Kir6.2KO) mouse which is defective in glucose-induced insulin secretion, and the other is a transgenic mouse expressing the tyrosine kinase-deficient (dominant-negative form of) human insulin receptor (hIR(KM)TG), and which has insulin resistance in muscle and fat. However, all of these mice have no evidence of overt diabetes. To determine if the double mutant Kir6.2KO/hIR(KM)TG mice would have diabetes, we generated mutant mice by crossbreeding, which would show both impaired glucose-induced insulin secretion and insulin resistance in muscle and fat. We report here that: 1) blood glucose levels of randomly fed and 6 h fasted double mutant (Kir6.2KO/hIR(KM)TG) mice were comparable with those of wild type mice; 2) in intraperitoneal glucose tolerance test (ipGTT), Kir6.2KO/hIR(KM)TG mice had an impaired glucose tolerance; and 3) during ipGTT, insulin secretion was not induced in either Kir6.2KO/hIR(KM)TG or Kir6.2KO mice, while the hIR(KM)TG mice showed a more prolonged insulin secretion than did wild type mice; 4) hyperinsulinemic euglycemic clamp test revealed that Kir6.2KO, Kir6.2KO/hIR(KM)TG and hIR(KM)TG mice, showed decreased whole-body glucose disposal compared with wild type mice; 5) Kir6.2KO, but not Kir6.2KO/hIR(KM)TG mice had some obesity and hyperleptinemia compared with wild type mice. Thus, the defects in glucose-induced insulin secretion (Kir6.2KO) and an insulin resistance in muscle and fat (hIR(KM)TG) were not sufficient to lead to overt diabetes.
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PMID:K(ATP) channel knockout mice crossbred with transgenic mice expressing a dominant-negative form of human insulin receptor have glucose intolerance but not diabetes. 1511 62

Insulin resistance is a common pathogenetic feature of type 2 diabetes. However, hyperglycemia would not develop if a concomitant defect in insulin secretion were not present. Impaired insulin secretion results from functional and survival defects of the beta-cell. The functional defects can be demonstrated early in the natural history of diabetes and they are hallmarked by abnormal pulsatility of basal insulin secretion and loss of first-phase insulin release in response to a glucose challenge. Moreover, a significant reduction of the beta-cell mass is apparent at the time of the diagnosis of diabetes. The progressive increase in glucose levels, that seems to characterize the natural history of type 2 diabetes, has been claimed to be largely due to progressive reduction of function and mass of beta-cells. Although a genetic predisposition is likely to account for impaired insulin secretion, chronic exposure to hyperglycemia and high circulating FFA is likely to contribute to both functional and survival defects. The disturbance in the endocrine activity of the pancreas is not limited to insulin, since a concomitant increase in fasting plasma glucagon and impaired suppression after the ingestion of an oral glucose load are often observed. This alteration becomes prominent after the ingestion of a mixed meal, when plasma glucagon remains much higher in the diabetic patient as compared to normal individuals. The disproportionate changes in the plasma concentration of the two pancreatic hormones is clearly evident when the insulin:glucagon molar ratio is considered. It is the latter that mainly affects hepatic glucose production. Because of the reduction of the insulin:glucagon molar ratio basal endogenous glucose concentration will be higher causing fasting hyperglycemia, while the hepatic glucose output will not be efficiently suppressed after the ingestion of a meal, contributing to excessive post-prandial glucose rise. Correcting beta- and alpha-cell dysfunction becomes, therefore, an attractive and rational therapeutic approach, particularly in the light of new treatments that may directly act on these pathogenetic mechanisms of type 2 diabetes.
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PMID:Beta- and alpha-cell dysfunction in type 2 diabetes. 1565 8


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