Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been known for some time that diabetes may be associated with impaired cognitive function. During the last decade, epidemiological data have emerged suggesting a linkage between diabetes, particularly type 2 diabetes, and Alzheimer's disease (AD). There is evidence to suggest that impaired activities of neurotrophic factors such as insulin, IGF-1 and NGF, which occur in both diabetes and AD, may provide a mechanistic link between the two disorders. An additional probable factor that has been less evaluated to date is hypercholesterolemia, a common accompaniment to type 2 diabetes. Increased cholesterol availability is believed to play a crucial role in the abnormal metabolism of amyloid precursor protein leading to accumulation of amyloid-beta. Impaired insulin signaling in particular appears to be involved in hyperphosphorylation of the tau protein, which constitutes neurofibrillary tangles in AD. The linkage between abnormal amyloid metabolism and phosphor-tau is likely to be provided by the activation of caspases both by increased amyloid-beta and by impaired insulin signaling. Although the details of many of these components still await evaluation, it appears clear that commonalities exist in the underlying pathogenesis of diabetes and Alzheimer's disease. In this review we provide a brief update on linkages between these two diverse but common disorders.
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PMID:Diabetes and Alzheimer's disease - is there a connection? 1748 40

To verify whether a diabetes family history might be a risk factor for the development, in adult age, of metabolic disorders, leptin, anthropometric and endocrine parameters were analysed in 95 babies with grandparents affected by type 2 diabetes (DF) and in 95 matched babies without diabetes family history (NDF). A sexual dimorphism for leptin was present in the NDF group (males: 6.7+/-4.1 ng/ml; females: 12.3+/-6.5; p < 0.0001) but not in the DF group (males: 9.0+/-5.5; females: 10.8+/-6.4), due to the significant increase in DF male leptin level, compared to that of NDF males (p < 0.05). In DF males only, leptin was positively correlated with body length, PI, C-peptide, IGF-1 and IGF1BP3. These results suggest that the increase in DF male leptin could be a compensatory mechanism for reduced insulin sensitivity in a pre-clinical alteration of glucose metabolism.
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PMID:Influence of family history of type 2 diabetes on leptin concentration in cord blood of male offspring with high birth weight. 1753 57

Hypertension commonly occurs in conjunction with insulin resistance and other components of the cardiometabolic syndrome. Insulin resistance plays a significant role in the relationship between hypertension, Type 2 diabetes mellitus, chronic kidney disease, and cardiovascular disease. There is accumulating evidence that insulin resistance occurs in cardiovascular and renal tissue as well as in classical metabolic tissues (i.e., skeletal muscle, liver, and adipose tissue). Activation of the renin-angiotensin-aldosterone system and subsequent elevations in angiotensin II and aldosterone, as seen in cardiometabolic syndrome, contribute to altered insulin/IGF-1 signaling pathways and reactive oxygen species formation to induce endothelial dysfunction and cardiovascular disease. This review examines currently understood mechanisms underlying the development of resistance to the metabolic actions of insulin in cardiovascular as well as skeletal muscle tissue.
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PMID:Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance. 1758 14

IGFs (insulin-like growth factors), which in an unbound form induce glucose and amino acid uptake, circulate bound to IGFBPs (IGF-binding proteins), which modulate their bioavailability and activity. The aim of the present study was to examine the effect of a standard meal [2301 kJ (550 kcal)] on the serum levels of IGFBP-1 in obese patients with T2DM (Type 2 diabetes mellitus), non-obese patients with T1DM (Type 1 diabetes mellitus) and healthy controls, using the artificial pancreas (Biostator) to obtain a normal glycaemic response to the meal. IGFBP-1 levels decreased by 50% over 2 h following the meal at a similar clearance in both the healthy controls and patients with T1DM, but no significant decline was seen in the patients with T2DM, despite a several-fold increase in insulin levels. The patients with T2DM were also studied during Sandostatin (somatostatin) infusion to decrease the inappropriate secretion of glucagon during the meal. During the 210 min of somatostatin infusion, the glucagon response was suppressed and IGFBP-1 levels were increased concomitantly with the peak in insulin levels, without any significant decrease after the meal. In conclusion, the impaired IGFBP-1 response to meal-related hyperinsulinaemia in obese patients with T2DM suggests a decreased availability of active IGF-1, leading to a decrease in glucose uptake during and after a meal in these patients. The stimulated meal response to glucagon, which contributes to postprandial hyperglycaemia, could not explain the increase in serum IGFBP-1 in these obese patients with T2DM.
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PMID:Postprandial paradoxical IGFBP-1 response in obese patients with Type 2 diabetes. 1820 2

Diabetic retinopathy continues to be the leading cause of legal blindness among working-age individuals. The earliest histological features of diabetic retinopathy include neuroretinal damage, capillary basement membrane thickening, loss of pericytes and loss of endothelial cells. At advanced stages, neovascularization, the hallmark of proliferative diabetic retinopathy (PDR) occurs, and blindness can result from relentless abnormal fibrovascular proliferation with subsequent bleeding and retinal detachment. Macular oedema is another retinal complication of diabetes that is responsible for a major part of vision loss, particularly in type 2 diabetes. The breakdown of the blood retinal barrier and the consequent vascular leakage and thickening of retina are the main events involved in its pathogenesis. Although a tight control of both blood glucose levels and hypertension are essential to prevent or arrest progression of the disease, the recommended goals are difficult to achieve in many patients. Laser photocoagulation treatment soon after the onset of PDR significantly reduces the incidence of severe vision loss. However, the optimal timing for laser treatment is frequently passed and, in addition, it is not uniformly successful in halting visual decline. For all these reasons, new pharmacological treatments based on the understanding of the pathophysiological mechanisms of diabetic retinopathy have been developed in recent years. There is mounting evidence to suggest that angiogenic factors play a crucial role in PDR development, vascular endothelial growth factor (VEGF) being the most relevant. Other growth factors or cytokines such as insulin-like growth factor I (IGF-1), hepatocyte growth factor (HGF), basic fibroblast growth factor (b-FGF), platelet derived growth factor (PDGF), pro-inflammatory cytokines and angiopoetins, are also involved in the pathogenesis of PDR. However, the intraocular synthesis of angiogenic factors is counterbalanced by the synthesis of antiangiogenic factors. Therefore, the balance between the angiogenic and antiangiogenic factors rather than angiogenic factors themselves will be crucial in determining the progression of PDR. The main antiangiogenic factor is the pigment epithelium derived factor (PEDF) but the transforming growth factor beta (TGF-beta), thrombospondin (TSP) and somatostatin are also among the intraocullary synthesized antiangiogenic factors.
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PMID:Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. 1822 Jun 19

Metformin, a first line treatment for type 2 diabetes, has been implicated as a potential anti-neoplastic agent for breast cancers as well as other cancers. Metformin is known to work in part through the activation of AMP-dependent kinase (AMPK). AMPK is a key regulator of cellular energy homeostasis, especially under stress conditions where biosynthetic pathways are blocked by the phosphorylation of downstream AMPK substrates. Stimulation of AMPK by metformin resulted in a significant repression of cell proliferation and active MAPK1/2 in both estrogen receptor alpha (ERalpha) negative (MDA-MB-231, MDA-MB-435) and positive (MCF-7, T47D) human breast cancer cell lines. However, when ERalpha negative MDA-MB-435 cells were treated with metformin, they demonstrated increased expression of vascular endothelial growth factor (VEGF) in an AMPK dependent manner; while the ERalpha positive MCF-7 cells did not. Systemic therapy with metformin was tested for efficacy in an orthotopic model of ERalpha negative breast cancer performed in athymic nude mice. Surprisingly, metformin therapy significantly improved tumorigenic progression as compared to untreated controls. The metformin-treated group showed increased VEGF expression, intratumoral microvascular density and reduced necrosis. Metformin treatment was sufficient, however, to reduce systemic IGF-1 and the proliferation rate of tumor cells in vascularized regions. The data presented here suggests that, although metformin significantly represses breast cancer cell growth in vitro, the efficacy with respect to its therapeutic application for ERalpha negative breast cancer lesions in vivo may result in promotion of the angiogenic phenotype and increased tumorigenic progression.
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PMID:Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERalpha negative MDA-MB-435 breast cancer model. 1825 28

Colorectal cancer occurs more frequently in patients with type 2 diabetes mellitus. The hyperinsulinemia-hypothesis suggests that elevated levels of insulin and free IGF-1 promote proliferation of colon cells and lead to a survival benefit of transformed cells, ultimately resulting in colorectal cancer. In patients with type 2 diabetes mellitus, epidemiological studies show an increased risk for colorectal cancer and an even higher risk if patients are treated with sulphonylureas or insulin. Moreover, tumour progression at hyperinsulinemia is more rapid and tumour-associated mortality is increased. Colorectal cancer can be avoided by screening. Recommendations for colorectal cancer screening should employ the recent epidemiologic evidence. All patients with type 2 diabetes mellitus should be recommended to undergo colonoscopy before starting insulin therapy, and screening intervals should not exceed 5 years. For this concept, a review of the evidence is presented, and a screening algorithm for colorectal cancer in patients with type 2 diabetes mellitus is proposed.
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PMID:Type 2 diabetes mellitus as risk factor for colorectal cancer. 1846 62

The study objective was to determine if Ramadan fasting was safe in patients with type 2 diabetes mellitus (T2D), based upon a determination of the effect of fasting on a broad range of physiological and clinical parameters, including markers of glycemic control and blood pressure. The study was carried out in Ramadan 1422 (December 2001-January 2002) at the Diabetology Services, Hopital Ibn Sina, Rabat, Morocco. One hundred and twenty T2D Moroccan patients (62 women, 58 men), aged 48-60 yrs with well-controlled diabetes through diet and/or oral hypoglycemic drugs (OHD), received dietary instructions and readjustment of the timing of the dose of OHD (gliclazide modified release) according to the fasting/eating periods. Anthropometric indices and physiological parameters (blood pressure, lipid, hematological, and serum electrolyte profiles, as well as markers of glycemic control, nutrition, renal and hepatic function) were measured on the day before Ramadan and then on the 15(th) and 29(th) day of fasting and thereafter 15 days later. Statistical analysis was done by standard methods. Ramadan fasting had no major effect on energy intake, body weight, body mass index, blood pressure, and liver enzymes. Fasting and post-prandial glucose levels decreased, while insulin levels increased. Diabetes was well controlled, as indicated by HbA1c, fructosamine, C-peptide, HOMA-IR, and IGF-1 values. There were fluctuations in some lipid and hematological parameters, creatinine, urea, uric acid, total protein, bilirubin, and electrolytes; however, all values stayed within the proper physiological range. In conclusion, diabetes was well-controlled in patients with dietary/medical management, without serious complications. With a regimen adjustment of OHD, diet control, and physical activity, most patients with T2D whose diabetes was well-controlled before Ramadan can safely observe Ramadan fasting.
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PMID:Is Ramadan fasting safe in type 2 diabetic patients in view of the lack of significant effect of fasting on clinical and biochemical parameters, blood pressure, and glycemic control? 1863 57

Recent studies have revealed that beta-cell dysfunction is an important factor in developing type 2 diabetes. beta-cell dysfunction is related to impairment of the insulin/IGF-1 signaling cascade through insulin receptor substrate-2 (IRS2). The induction of IRS2 in beta-cells plays an important role in potentiating beta-cell function and mass. In this study, we investigated whether herbs used for treating diabetes in Chinese medicine-Galla rhois, Rehmanniae radix, Machilus bark, Ginseng radix, Polygonatum radix, and Scutellariae radix-improved IRS2 induction in rat islets, glucose-stimulated insulin secretion and beta-cell survival. R. radix, Ginseng radix and S. radix significantly enhanced glucose-stimulated insulin secretion compared to the control, i.e., by 49, 67 and 58%, respectively. These herbs induced the expression of IRS2, pancreas duodenum homeobox-1 (PDX-1), and glucokinase. The increased level of glucokinase could explain the enhancement of glucose-stimulated insulin secretion with these extracts. Increased PDX-1 expression was associated with beta-cell proliferation, which was consistent with the cell viability assay. In conclusion, R. radix, Ginseng radix and S. radix had an insulinotropic action similar to that of exendin-4.
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PMID:Extracts of Rehmanniae radix, Ginseng radix and Scutellariae radix improve glucose-stimulated insulin secretion and beta-cell proliferation through IRS2 induction. 1885 Feb 29

Twenty Simmental x Angus, half-sibling, postpubertal heifers (initial BW of 443 +/- 9 kg) were allotted randomly into 2 treatment groups to evaluate if initial BCS affects response of the hypothalamic-pituitary-ovarian axis to metabolic signals elicited by energy restriction and repletion. During a preliminary feeding period, diets were formulated so that each heifer in the designated treatment would reach a BCS of 5 (moderate condition; MOD) or a BCS of 7 (heavy condition; FAT). Once each heifer had reached desired BCS, diets were formulated to supply 30% of NE(m) requirements until each heifer became anestrous (serum concentrations of progesterone < 1 ng/mL; restriction period). Blood collections took place on d 1 of each period, on d 43 of energy restriction and d 44 of energy repletion, and when heifers were confirmed to recommence estrous cycles. When heifers were cycling, their estrous cycles were synchronized to ensure hormone sampling occurred during late diestrus or early proestrus. Energy restriction resulted in decreased concentrations of LH (FAT, P = 0.02; MOD, P < 0.001), IGF-1 (FAT, P < 0.001; MOD, P = 0.003), and insulin (P < 0.001); in contrast, concentrations of GH (P < 0.001) and plasma urea nitrogen (P < 0.001) increased. During repletion, LH concentration increased (P = 0.03) in MOD condition heifers but was still less (P = 0.002) than d 1 of restriction, whereas LH concentration tended to increase in FAT heifers (P = 0.06) until it was similar (P = 0.40) to d 1 of restriction. Repletion also increased concentrations of IGF-1 (P < 0.001), insulin (P < 0.001), and glucose (P < 0.001), whereas concentrations of GH (P < 0.001), NEFA (P < 0.001), and plasma urea nitrogen (P < 0.001) decreased. For both treatments, concentrations of GH after repletion were similar (FAT, P = 0.88; MOD, P = 0.10) to those on d 1 of restriction. After repletion, FAT condition heifers had decreased concentrations of IGF-1 (P < 0.001), insulin (P < 0.05), and glucose (P < 0.001), but greater concentrations of acetate (P < 0.01) and butyrate (P < 0.05), than MOD heifers. Anestrus or resumption of estrous cycles seems to be activated gradually in response to dietary manipulation, unrelated to certain metabolite changes.
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PMID:Initial body condition score affects hormone and metabolite response to nutritional restriction and repletion in yearling postpubertal beef heifers. 1935 2


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