β-cell dysfunction and insulin resistance in type 2 diabetes: role of metabolic and genetic abnormalities

TL;DR: The novel acylated analogue, insulin detemir, appears to lack the usual propensity for causing weight gain and elucidation of the pharmacological mechanisms underlying this property might help clarify the mechanisms linking insulin with weight regulation.

TL;DR: In vitro study of islet function from diabetic patients revealed an abnormal glucose-stimulated insulin release response in perifusion assays, and an equivalent number of type 2 diabetic islets failed to reverse hyperglycemia when transplanted to immunodeficient diabetic mice.

TL;DR: In this article, it was found that persistent hyperglycemia caused the functional decline of neutrophils, which is a life-threatening risk factor for infection, not only in the chronic but also in the acute phase.

TL;DR: How circulating factors such as insulin itself, TNF-α, interleukins, fatty acids and glycation products influence insulin action through insulin signalling molecules themselves or through other pathways ultimately impinging on the insulin-signalling pathway is reviewed.

TL;DR: Clinical intervention studies have demonstrated that reduction in the chronic microvascular and macrovascular complications of type 2 diabetes requires treatment of hyperglycemia, and oral antihyperglycemic agents increase endogenous insulin secretion, decrease insulin resistance, or lower postprandial plasma glucose rise by delaying absorption of complex carbohydrates.

TL;DR: The data suggest that the poor insulin response in overt diabetes results not only from an inherent insensitivity of B-cells to glucose but also from the metabolic derangement of diabetes.

TL;DR: If the hypothesis is correct that common signaling abnormalities in the metabolism of malonyl-CoA and LC- CoA contribute to altered insulin release and sensitivity, it offers a novel explanation for the presence of variable combinations of these defects in individuals with differing genetic backgrounds.

TL;DR: The literature better supports the case of impaired insulin secretion being the initial and main genetic factor predisposing to type 2 diabetes, especially the studies in people at high risk to subsequently develop type 1 diabetes and the studies demonstrating compete alleviation of insulin resistance with weight loss.