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Gene Review:

T2dm1 - type 2 diabetes mellitus 1

Mus musculus

This record was replaced with 207227.

Mootha, V.K. et al., Martín-Campos, J.M. et al., Erdei, N. et al., Bagi, Z. et al., Nadler, S.T. et al., et al.

Wolfram, Raederstorff, Preller, Wang, Teixeira, Riegger, Weber, Höppener, Ahrén, Lips, Perry, Lahiri, Sambamurti, Chen, Mattson, Egan, Greig, Mootha, Handschin, Arlow, Xie, St Pierre, Sihag, Yang, Altshuler, Puigserver, Patterson, Willy, Schulman, Heyman, Lander, Spiegelman, Budde, Schulte, Appel, Neitz, Kellmann, Tammen, Hess, Rose, Clemmons, Okamoto, Takemori, Katoh,

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Disease relevance of T2dm1

Obesity, hyperlipidemia, and insulin resistance are common forerunners of type 2 diabetes mellitus [1].
Deletion of the gene encoding p27(Kip1) (Cdkn1b) ameliorated hyperglycemia in these animal models of type 2 diabetes mellitus by increasing islet mass and maintaining compensatory hyperinsulinemia, effects that were attributable predominantly to stimulation of pancreatic beta-cell proliferation [2].
Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1alpha) develop dwarfism, liver dysfunction, and type 2 diabetes mellitus [3].
SUMMARY: An increased plasma concentration of apoA-II might contribute to familial combined hyperlipidemia or type 2 diabetes mellitus expression, which emphasizes the need to understand its function and metabolism [4].
OBJECTIVE: A novel lipodystrophy syndrome characterized by truncal adiposity, peripheral fat atrophy, type 2 diabetes mellitus, and dyslipidemia occurs in HIV-infected individuals, and may be aggravated by HIV-1 protease inhibitors [5].

Psychiatry related information on T2dm1

Two substrates of insulin-degrading enzyme (IDE), amyloid beta-protein (Abeta) and insulin, are critically important in the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2), respectively [6].

High impact information on T2dm1

Our identification of the Sorcs1 gene provides insight into the pathway underlying the pathophysiology of obesity-induced type 2 diabetes mellitus [7].
Islet amyloid and type 2 diabetes mellitus [8].
Obesity is closely associated with insulin resistance and establishes the leading risk factor for type 2 diabetes mellitus, yet the molecular mechanisms of this association are poorly understood [9].
The observed phenotype closely parallels those of preclinical type 2 diabetes mellitus, in which malnutrition-induced hypoinsulinaemia predisposes individuals to glucose intolerance [10].
In addition to insulin resistance, all three subjects developed type 2 diabetes mellitus and hypertension at an unusually early age [11].

Chemical compound and disease context of T2dm1

Obesity is strongly correlated with type 2 diabetes mellitus, a common disorder of glucose and lipid metabolism [12].
This study investigated the antidiabetic effects of the most abundant green tea catechin, epigallocatechin gallate (EGCG, TEAVIGO), in rodent models of type 2 diabetes mellitus and H4IIE rat hepatoma cells [13].
Therefore, either abnormal levels of endogenous estrogens or environmental estrogen exposure enhances the risk of developing type 2 diabetes mellitus, hypertension, and dyslipidemia [14].
We tested the hypothesis that short-term treatment of mice with Type 2 diabetes mellitus (DM) with rosiglitazone (ROSI), an agonist of peroxisome proliferator-activated receptor-gamma, ameliorates the impaired coronary arteriolar dilation by reducing oxidative stress via a mechanism unrelated to its effect on hyperglycemia and hyperinsulinemia [15].
We examined the effects of the angiotensin-II receptor antagonist candesartan on non-alcoholic fatty liver (NAFL) and circulating adiponectin concentrations in KKAy obese mice with type 2 diabetes mellitus [16].

Biological context of T2dm1

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates fat-cell development and glucose homeostasis and is the molecular target of a class of insulin-sensitizing agents used for the management of type 2 diabetes mellitus [17].
Linkage disequilibrium analysis revealed that the -420G/G genotype itself was a primary variant determining T2DM susceptibility [18].
Our data show that a decrease in expression of genes normally involved in adipogenesis is associated with obesity, and we further identify genes important for subsequent development of type 2 diabetes mellitus [12].
Oxygen free radicals have been implicated in beta-cell dysfunction and apoptosis associated with type 1 and type 2 diabetes mellitus [19].
This, and the location of the apoA-II gene in chromosome 1q23, a hot region in the search for genes associated with familial combined hyperlipidemia, insulin resistance and type 2 diabetes mellitus, has greatly increased interest in this protein [4].

Anatomical context of T2dm1

Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to alterations in fat metabolism [20].
Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene cause maturity onset diabetes of the young type 3, a form of type 2 diabetes mellitus [21].
Insulin receptor substrate-2-dependent interleukin-4 signaling in macrophages is impaired in two models of type 2 diabetes mellitus [22].
This finding, along with the fact that its expression is raised in the white adipose tissue of mice with type 2 diabetes mellitus, suggests that SIK2 might be involved in metabolic regulation in adipose tissue [23].
It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion and lowers blood glucose and food intake in patients with type 2 diabetes mellitus [24].

Associations of T2dm1 with chemical compounds

Pioglitazone mitigates renal glomerular vascular changes in high-fat, high-calorie-induced type 2 diabetes mellitus [25].
Metformin, a biguanide, is widely used as an oral hypoglycemic agent for the treatment of type 2 diabetes mellitus [26].
We hypothesized that, in mice with T2-DM, hydrogen peroxide (H(2)O(2)) is involved in the increased synthesis of constrictor prostaglandins, hence enhanced basal tone in skeletal muscle arterioles [27].
Thus we propose that, in mice with T2-DM, arteriolar production of H(2)O(2) is enhanced, which leads to increased synthesis of the constrictor prostaglandins thromboxane A(2)/prostaglandin H(2) in the smooth muscle cells, which enhance basal arteriolar tone [27].
Troglitazone (Tro), one of the thiazolidinediones, is a novel antidiabetic agent for patients with type 2 diabetes mellitus [28].

Physical interactions of T2dm1

The G/G genotype of a resistin single-nucleotide polymorphism at -420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3 [18].

Regulatory relationships of T2dm1

Thiazolidinediones (TZDs) increase peripheral tissue insulin sensitivity in patients with type 2 diabetes mellitus by activating the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) [29].

Other interactions of T2dm1

Overt hyperglycemia and type 2 diabetes mellitus can be manifested in states of leptin signaling deficiencies by the additional effects of other genetic factors [30].
Administration of IGF-I to patients with type 2 diabetes mellitus has been shown to result in an improvement in insulin sensitivity and a reduction in the requirement for exogenously administered insulin to maintain glucose homeostasis [31].
These results illustrate the dissection of gene regulatory networks in a complex mammalian system, elucidate the mechanism of PGC-1alpha action in the OXPHOS pathway, and suggest that Erralpha agonists may ameliorate insulin-resistance in individuals with type 2 diabetes mellitus [32].
Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathogenesis of obesity-driven type 2 diabetes mellitus and associated cardiovascular complications [33].
Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity [34].

Analytical, diagnostic and therapeutic context of T2dm1

Denaturing high-performance liquid chromatography (DHPLC) was used to search for sequence variants in DNA from 259 T2DM individuals [35].
In contrast to immunoassays, unbiased proteomic technologies provide the opportunity to screen for novel marker protein and peptides of T2DM [36].
METHODS: Oral glucose tolerance tests (OGTT) and biochemical assays for plasma insulin, lipid profiles and serum visfatin were performed in 241 newly diagnosed T2DM patients, subjects with impaired glucose regulation (IGR), and normal glucose tolerant subjects more than 40 years of age [37].
The complex showed a tendency to lower the high blood glucose levels of KK-A(y) mice with type 2 diabetes mellitus when given by oral administration at a dose of 20 mg Zn/kg body weight for 16 d [38].
The high blood glucose level of KK-Ay mice with type 2 diabetes mellitus was lowered by daily intraperitoneal injections of a zinc(II) complex, cis-[Zn(L-Thr)2(H2O)2], for 14 d [39].

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