Insulin action and resistance in obesity and type 2 diabetes
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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.read more
Citations
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Mechanisms of Insulin Action and Insulin Resistance
TL;DR: This work aims to develop an integrated physiological perspective, placing the intricate signaling effectors that carry out the cell-autonomous response to insulin in the context of the tissue-specific functions that generate the coordinated organismal response.
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Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications
Michele Longo,Federica Zatterale,Federica Zatterale,Jamal Naderi,Jamal Naderi,Luca Parrillo,Luca Parrillo,Pietro Formisano,Pietro Formisano,Gregory Alexander Raciti,Gregory Alexander Raciti,Francesco Beguinot,Francesco Beguinot,Claudia Miele,Claudia Miele +14 more
TL;DR: A better understanding of the mechanisms regulating adipose tissue expansion in obesity is required for the development of future therapeutic approaches in obesity-associated metabolic complications.
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Pathophysiology of Type 2 Diabetes Mellitus.
Unai Galicia-Garcia,Asier Benito-Vicente,Shifa Jebari,Asier Larrea-Sebal,Haziq Siddiqi,Kepa B. Uribe,Helena Ostolaza,César Martín +7 more
TL;DR: This review analyzes the key aspects of type 2 Diabetes Mellitus, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance, and summarizes the data gathered up until now.
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The integrative biology of type 2 diabetes.
Michael Roden,Gerald I. Shulman +1 more
TL;DR: Recent studies providing insights into insulin resistance and increased hepatic gluconeogenesis associated with obesity and type 2 diabetes are summarized, focusing on data from humans and relevant animal models.
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Biochemical and cellular properties of insulin receptor signalling
TL;DR: In the past decade, major progress has led to the delineation of mechanisms of glucose transport, lipid synthesis, storage and mobilization, which will accelerate the discovery of new treatment modalities for diabetes.
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