Current views on type 2 diabetes

Type 2 diabetes mellitus (T2DM) affects a large population worldwide. T2DM is a complex heterogeneous group of metabolic disorders including hyperglycemia and impaired insulin action and/or insulin secretion. T2DM causes dysfunctions in multiple organs or tissues. Current theories of T2DM include a defect in insulin-mediated glucose uptake in muscle, a dysfunction of the pancreatic β-cells, a disruption of secretory function of adipocytes, and an impaired insulin action in liver. The etiology of human T2DM is multifactorial, with genetic background and physical inactivity as two critical components. The pathogenesis of T2DM is not fully understood. Animal models of T2DM have been proved to be useful to study the pathogenesis of, and to find a new therapy for, the disease. Although different animal models share similar characteristics, each mimics a specific aspect of genetic, endocrine, metabolic, and morphologic changes that occur in human T2DM. The purpose of this review is to provide the recent progress and current theories in T2DM and to summarize animal models for studying the pathogenesis of the disease.

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Animal models of catheter-induced intimal hyperplasia in type 1 and type 2 diabetes and the effects of pharmacologic intervention

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-098 ◽

2009 ◽

Vol 87 (1) ◽

pp. 37-50 ◽

Cited By ~ 8

Author(s):

D.B. McNamara ◽

S.N. Murthy ◽

A.N. Fonseca ◽

C.V. Desouza ◽

P.J. Kadowitz ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Animal Models ◽

Vascular Injury ◽

Intimal Hyperplasia ◽

In Vivo Studies ◽

Impaired Insulin

Diabetes is a complex disorder characterized by impaired insulin formation, release or action (insulin resistance), elevated blood glucose, and multiple long-term complications. It is a common endocrine disorder of humans and is associated with abnormalities of carbohydrate and lipid metabolism. There are two forms of diabetes, classified as type 1 and type 2. In type 1 diabetes, hyperglycemia is due to an absolute lack of insulin, whereas in type 2 diabetes, hyperglycemia is due to a relative lack of insulin and insulin resistance. More than 90% of people with diabetes have type 2 with varied degrees of insulin resistance. Insulin resistance is often associated with impaired insulin secretion, and hyperglycemia is a common feature in both types of diabetes, but failure to make a distinction between the types of diabetes in different animal models has led to confusion in the literature. This is particularly true in relation to cardiovascular disease in the presence of diabetes and especially the response to vascular injury, in which there are major differences between the two types of diabetes. Animal models do not completely mimic the clinical disease seen in humans. Animal models are at best analogies of the pathologic process they are designed to represent. The focus of this review is an analysis of intimal hyperplasia following catheter-induced vascular injury, including factors that may complicate comparisons between different animal models or between in vitro and in vivo studies. We examine the variables, pitfalls, and caveats that follow from the manner of induction of the injury and the diabetic state of the animal. The efficacy of selected antidiabetic drugs in inhibiting the development of the hyperplastic response is also discussed.

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Mouse models of insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00561.2001 ◽

2002 ◽

Vol 282 (5) ◽

pp. E977-E981 ◽

Cited By ~ 40

Author(s):

Marta Letizia Hribal ◽

Francesco Oriente ◽

Domenico Accili

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Insulin Signaling ◽

Insulin Action ◽

Β Cells ◽

Β Cell ◽

Pancreatic Β Cells ◽

Impaired Insulin

The hallmarks of type 2 diabetes are impaired insulin action in peripheral tissues and decreased pancreatic β-cell function. Classically, the two defects have been viewed as separate entities, with insulin resistance arising primarily from impaired insulin-dependent glucose uptake in skeletal muscle, and β-cell dysfunction arising from impaired coupling of glucose sensing to insulin secretion. Targeted mutagenesis and transgenesis involving components of the insulin action pathway have changed our understanding of these phenomena. It appears that the role of insulin signaling in the pathogenesis of type 2 diabetes has been overestimated in classic insulin target tissues, such as skeletal muscle, whereas it has been overlooked in liver, pancreatic β-cells, and brain, which had been thought not to be primary insulin targets. We review recent progress and try to reconcile areas of apparent controversy surrounding insulin signaling in skeletal muscle and pancreatic β-cells.

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