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

Ethanol has been considered as a lifestyle factor that may influence the risk of type 2 diabetes mellitus. In healthy adults, acute ethanol consumption results in insulin resistance. Acute ethanol consumption causes insulin resistance selectively in skeletal muscle by an indirect mechanism. Possible mediators include triglycerides (TGs), catecholamines, acetaldehyde, alterations in insulin binding, and hepatic insulin sensitizing substance (HISS). Recent studies in rats showed that acute administration of ethanol causes insulin resistance in a dose-dependent manner that is secondary to the blockade of insulin-induced HISS release. Chronic ethanol consumption may improve insulin sensitivity, but the results from the randomized controlled trials are mixed. Differences in ethanol dose, consumption period, and abstention period may account for the discrepant results. Epidemiological studies have suggested that the relationship between ethanol and insulin sensitivity is either an inverted U-shape or a positive linear relationship. Future randomized controlled trials should consider the dose of ethanol and the duration of ethanol consumption and abstention in the experimental design. Chronic prenatal and postnatal (nursing) ethanol exposure results in insulin resistance that is secondary to the absence of HISS release/action with the HISS-independent insulin action and insulin-like growth factor-1 (IGF-1)-mediated glucose disposal action remaining unimpaired. The impaired HISS release may be related to a reduction in hepatic glutathione (GSH) levels. The effect of chronic ethanol consumption on HISS has not been evaluated.
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PMID:The effect of acute, chronic, and prenatal ethanol exposure on insulin sensitivity. 1631 Feb 55

The total mass of islets of Langerhans is reduced in individuals with type 2 diabetes, possibly contributing to the pathogenesis of this condition. Although the regulation of islet mass is complex, recent studies have suggested the importance of a signaling pathway that includes the insulin or insulin-like growth factor-1 receptors, insulin receptor substrate and phosphatidylinositol (PI) 3-kinase. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a serine-threonine kinase that mediates signaling downstream of PI 3-kinase. Here we show that mice that lack PDK1 specifically in pancreatic beta cells (betaPdk1-/- mice) develop progressive hyperglycemia as a result of a loss of islet mass. The mice show reductions in islet density as well as in the number and size of cells. Haploinsufficiency of the gene for the transcription factor Foxo1 resulted in a marked increase in the number, but not the size, of cells and resulted in the restoration of glucose homeostasis in betaPdk1-/- mice. These results suggest that PDK1 is important in maintenance of pancreatic cell mass and glucose homeostasis.
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PMID:Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass. 1664 23

The evolutionarily conserved phosphoinositide 3-kinase (PI3K) signaling pathway mediates both the metabolic effects of insulin and the growth-promoting effects of insulin-like growth factor-1 (IGF-1). We have generated mice deficient in both the p85alpha/p55alpha/p50alpha and the p85beta regulatory subunits of class I(A) PI3K in skeletal muscles. PI3K signaling in the muscle of these animals is severely impaired, leading to a significant reduction in muscle weight and fiber size. These mice also exhibit muscle insulin resistance and whole-body glucose intolerance. Despite their ability to maintain normal fasting and fed blood glucose levels, these mice show increased body fat content and elevated serum free fatty acid and triglyceride levels. These results demonstrate that in vivo p85 is a critical mediator of class I(A) PI3K signaling in the regulation of muscle growth and metabolism. Our finding also indicates that compromised muscle PI3K signaling could contribute to symptoms of hyperlipidemia associated with human type 2 diabetes.
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PMID:Loss of class IA PI3K signaling in muscle leads to impaired muscle growth, insulin response, and hyperlipidemia. 1667 93

There are only a few data on the relationship of insulin-like growth factor-1 (IGF-1), implicated in glucose homeostasis, and C-reactive protein (CRP), a measure of subclinical systemic inflammation, in patients with the metabolic syndrome (MetS). The authors investigated, in a cross-sectional design, the correlation between total IGF-1 and CRP in 170 subjects. Among them 123 had the MetS (National Cholesterol Program ATP III definition) and 47 did not, and 136 had type 2 diabetes mellitus (DM) and 34 did not. Anthropometric variables, clinical characteristics, as well as laboratory measurements, including total IGF-1 and CRP, were recorded. CRP levels showed a significant negative correlation with total IGF-1 concentrations, both in the whole study population (r = -0.252, p = 0.001) and the MetS group (r = -0.203, p = 0.025), regardless of the presence of DM. This correlation remained significant after adjusting for age, gender, smoking status, and waist circumference (r = -0.18, p = 0.05). Both low IGF-1 and high CRP levels had an almost linear relationship with the number of MetS components (p = 0.029 and p = 0.020, respectively), suggesting a close relationship of both variables with the cardiovascular disease (CVD) risk involved. The correlation between high CRP and low total IGF-1 might indicate that an increase in CRP levels may well be a key factor for the reduction in IGF-1 concentrations. Both factors are related to an increase in risk for MetS and CVD and this finding might have clinical implications in preventing or treating MetS, DM, and CVD. Given the cross-sectional design of the study, this finding should be confirmed by larger prospective and, it is hoped, interventional studies.
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PMID:Total serum insulin-like growth factor-1 and C-reactive protein in metabolic syndrome with or without diabetes. 1670 90

Most of the basic components of the metabolic syndrome, namely type 2 diabetes mellitus, hypertension, obesity, or low high-density lipoprotein cholesterol levels, apart from being major risk factors for cardiovascular disease have been also associated with an increased risk of chronic kidney disease. However, several epidemiologic studies conducted over the past years suggest that the central component of the syndrome, insulin resistance, as well as compensatory hyperinsulinemia are independently associated with an increased prevalence of chronic kidney disease. In addition, background studies support the existence of several pathways linking insulin resistance and hyperinsulinemia with kidney damage. Insulin per se promotes the proliferation of renal cells and stimulates the production of other important growth factors such as insulin-like growth factor-1 and transforming growth factor beta. Insulin also upregulates the expression of angiotensin II type 1 receptor in mesangial cells, thus enhancing the deleterious effects of angiotensin II in the kidney, and stimulates production and renal action of endothelin-1. Moreover, insulin resistance and hyperinsulinemia are associated with decreased endothelial production of nitric oxide and increased oxidative stress which have been also implicated in the progression of diabetic nephropathy. This review analyzes the above and other potential mechanisms, through which insulin resistance and hyperinsulinemia can contribute to renal injury.
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PMID:Insulin resistance, hyperinsulinemia, and renal injury: mechanisms and implications. 1673 48

Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory disease of skeleton characterized by hyperostosis of axial and peripheral skeleton. The association of DISH with type 2 diabetes mellitus and other metabolic alterations (e.g. impaired lipid metabolism) has been known for many years. However, it has not been explained satisfactorily yet. It seems that this pathological process is significantly influenced by hyperglycemia and insulin resistance. Also, it is affected by growth hormone (GH) and its action mediated by insulin-like growth factor (IGF) and its binding proteins (IGFBP2, IGFBP3). From the point of symptomatic therapy, patients should not be given medicaments that aggravate hyperinsulinemia.
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PMID:[Diffuse idiopathic skeletal hyperostosis and its relation to metabolic parameters]. 1677 Oct 94

Acromegaly is caused by excessive secretion of growth hormone (GH), and a resultant persistent elevation of insulin-like growth factor-1 (IGF-1) levels. Diabetes mellitus is accompanied in some acromegalic patients with insulin resistance. We encountered a type-2 diabetic patient who had a poorly controlled glycemic state and was diagnosed as acromegaly with normal IGF-1 levels. The patient showed definite acromegalic features. However, in the first screening test, GH levels were high and IGF-1 levels were inappropriately normal so the results were not close to the diagnosis of acromegaly. After moderate glycemic control, an oral glucose suppression test was performed, showing no suppressed GH response. TRH test revealed paradoxical increases in growth hormone levels and a brain MRI discovered a pituitary adenoma. After several-months insulin treatment, IGF-1 levels were increased to the abnormal state and GH levels were decreased without treatment for acromegaly. Here we report the rare case of acromegaly that presents inappropriately normal IGF-1 levels at the time of diagnosis in uncontrolled type 2 diabetic patient and shows increased IGF-1 levels after glycemic control with insulin therapy. When evaluating acromegaly in type 2 diabetes under poorly controlled glycemia, cautious IGF-1 analysis is needed after sufficient glycemic control.
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PMID:Acromegaly associated with type 2 diabetes showing normal IGF-1 levels under poorly controlled glycemia. 1757 66

No mouse model is currently available where the induction of type 2 diabetes on an atherosclerotic background could be achieved without significant concomitant changes in plasma lipid levels. We crossbred 2 genetically modified mouse strains to achieve a model expressing both atherosclerosis and characteristics of type 2 diabetes. For atherosclerotic background we used low-density lipoprotein receptor-deficient mice synthetizing only apolipoprotein B100 (LDLR(-/-) ApoB(100/100)). Diabetic background was obtained from transgenic mice overexpressing insulin-like growth factor-II (IGF-II) in pancreatic beta cells. Thorough phenotypic characterization was performed in 6- and 15-month-old mice on both normal and high-fat Western diet. Results indicated that IGF-II transgenic LDLR(-/-)ApoB(100/100) mice demonstrated insulin resistance, hyperglycemia, and mild hyperinsulinemia compared with hypercholesterolemic LDLR(-/-)ApoB(100/100) controls. In addition, old IGF-II/LDLR(-/-)ApoB(100/100) mice displayed significantly increased lesion calcification, which was more related to insulin resistance than glucose levels, and significantly higher baseline expression in aorta of several genes related to calcification and inflammation. Lipid levels of IGF-II/LDLR(-/-)ApoB(100/100) mice did not differ from LDLR(-/-)ApoB(100/100) controls at any time. In conclusion, type 2 diabetic factors induce increased calcification and lesion progression without any lipid changes in a new mouse model of diabetic macroangiopathy.
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PMID:Increased atherosclerotic lesion calcification in a novel mouse model combining insulin resistance, hyperglycemia, and hypercholesterolemia. 1787 64

Most patients with type 2 diabetes mellitus will eventually require insulin therapy to achieve or maintain adequate glycaemic control. The introduction of insulin analogues, with pharmacokinetics that more closely mimic endogenous insulin secretion, has made physiologic insulin replacement easier to achieve for many patients. However, there are also concerns regarding alteration of binding affinities for the insulin receptor (IR) or insulin-like growth factor-1 receptor (IGF-1R) may increase the mitogenic potential of some analogues. Therefore, this article will review the relevant preclinical and clinical data to assess the mitogenic potential of insulin glargine, a basal insulin analogue, compared with regular human insulin (RHI). Searches of the PubMed database were performed using terms that included 'IR,' 'insulin-like growth factor-1,' 'IGF-1R,' 'type 2 diabetes mellitus,' and 'insulin glargine.' Original articles and reviews of published literature were retrieved and reviewed. Although one study reported increased binding affinity of insulin glargine for the IGF-1R and increased mitogenic potential in cells with excess IGF-1Rs (Saos/B10 osteosarcoma cells), most in vitro binding-affinity and cell-culture studies have demonstrated behaviour of insulin glargine comparable to that of RHI for both IR and IGF-1R binding, insulin signalling, and metabolic and mitogenic potential.Currently published in vivo carcinogenic studies and human clinical trial data have shown that insulin glargine is not associated with increased risk for either cancer or the development or progression of diabetic retinopathy.
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PMID:Insulin glargine and receptor-mediated signalling: clinical implications in treating type 2 diabetes. 1792 76

A wide range of genetically engineered murine models of type 2 diabetes have been created to try to understand the site of the primary defect in insulin action, and the relationship between insulin resistance and impaired beta-cell function in diabetes. Genetic disruption of various aspects known to be important in diabetes has examined specific facets, including glucose sensing, transcription factors for the insulin gene, the insulin gene itself, insulin and insulin-like growth factor receptors, downstream signaling components and some mutations that increase insulin sensitivity. This article focuses on models that have given insight into insulin resistance and impaired insulin production, especially models that examine molecules involved in the signaling pathway downstream of insulin binding its receptor. These models recapitulate many features of human type 2 diabetes and, although they have emphasized the complexity of this disease, they offer numerous opportunities to characterize particular aspects and eventually fit them together to help delineate the human disease.
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PMID:Mechanisms of disease: using genetically altered mice to study concepts of type 2 diabetes. 1821 63


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