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Insulin action and resistance in obesity and type 2 diabetes

Michael P. Czech
- 01 Jul 2017 - 
- Vol. 23, Iss: 7, pp 804-814
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TLDR
This Perspective reviews alternate viewpoints and recent results on the temporal and mechanistic connections between hyperinsulinemia, obesity and insulin resistance and connects insulin resistance to extensive metabolic cross-talk between the liver, adipose tissue, pancreas and skeletal muscle.
Abstract
Nutritional excess is a major forerunner of type 2 diabetes. It enhances the secretion of insulin, but attenuates insulin's metabolic actions in the liver, skeletal muscle and adipose tissue. However, conflicting evidence indicates a lack of knowledge of the timing of these events during the development of obesity and diabetes, pointing to a key gap in our understanding of metabolic disease. This Perspective reviews alternate viewpoints and recent results on the temporal and mechanistic connections between hyperinsulinemia, obesity and insulin resistance. Although much attention has addressed early steps in the insulin signaling cascade, insulin resistance in obesity seems to be largely elicited downstream of these steps. New findings also connect insulin resistance to extensive metabolic cross-talk between the liver, adipose tissue, pancreas and skeletal muscle. These and other advances over the past 5 years offer exciting opportunities and daunting challenges for the development of new therapeutic strategies for the treatment of type 2 diabetes.

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References
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Pathogenesis of NIDDM: A balanced overview

TL;DR: Information concerning the loss of first-phase insulin secretion, altered pulsatility of insulin release, and enhanced proinsulin-insulin secretory ratio is discussed as it pertains to altered β-cell function in NIDDM.
Journal ArticleDOI

Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes

TL;DR: It is postulate that this variability in the severity of insulin resistance varies greatly among obese people might reflect differences in levels of lipid-droplet proteins that promote the sequestration of fatty acids within adipocytes in the form of triglycerides, thereby lowering exposure of skeletal muscle to the inhibitory effects of fatty acid.
Journal ArticleDOI

Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ)

TL;DR: It is shown that mice deficient in Akt2 are impaired in the ability of insulin to lower blood glucose because of defects in the action of the hormone on liver and skeletal muscle, establishing Akt 2 as an essential gene in the maintenance of normal glucose homeostasis.
Journal ArticleDOI

ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation

TL;DR: It is found that ACL is required for increases in histone acetylation in response to growth factor stimulation and during differentiation, and that glucose availability can affect hist one acetylations in an ACL-dependent manner.
Journal ArticleDOI

Insulin Receptor Signaling in Normal and Insulin-Resistant States

TL;DR: In the wake of the worldwide increase in type-2 diabetes, a major focus of research is understanding the signaling pathways impacting this disease, which are essential for development of new drugs to treat diabetes, metabolic syndrome, and their complications.
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How long does it take to regulate insulin resistance?

Although much attention has addressed early steps in the insulin signaling cascade, insulin resistance in obesity seems to be largely elicited downstream of these steps.