Insulin action and resistance in obesity and type 2 diabetes
Reads0
Chats0
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
More filters
Journal ArticleDOI
Global Analysis of miRNA Signature Differentially Expressed in Insulin-resistant Human Hepatocellular Carcinoma Cell Line
TL;DR: The present study demonstrated the possible miRNAs and predicted target genes involving in the pathophysiology of insulin resistant HCC, providing novel insights into the molecular mechanisms of multidrug resistance in the insulin resistant HepG2 cells.
Journal ArticleDOI
GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo
Alba C. Arcones,Rocío Vila-Bedmar,Mercedes Mirasierra,Marta Cruces-Sande,Mario Vallejo,Ben Jones,Alejandra Tomas,Federico Mayor,Cristina Murga +8 more
TL;DR: In this paper, the role of GRK2 as a regulator of incretin-mediated insulin secretion in vivo has been investigated and shown to be important for β-arrestin recruitment.
Journal ArticleDOI
A colorimetric bioassay for quantitation of both basal and insulin-induced glucose consumption in 3T3-L1 adipose cells.
TL;DR: A simple and low-cost bioassay is proposed to quantify glucose consumption in 3T3-L1 adipose cells by observing a linear response over time to the different glucose concentrations, both in the basal and insulin-induced condition.
Journal ArticleDOI
Glycoursodeoxycholic acid ameliorates diet-induced metabolic disorders with inhibiting endoplasmic reticulum stress.
Lele Cheng,Tao Chen,Tao Chen,Manyun Guo,Manyun Guo,Peining Liu,Peining Liu,Xiangrui Qiao,Xiangrui Qiao,Yuanyuan Wei,Yuanyuan Wei,Jianqing She,Jianqing She,Bolin Li,Bolin Li,Wen Xi,Juan Zhou,Juan Zhou,Zuyi Yuan,Zuyi Yuan,Yue Wu,Yue Wu,Junhui Liu +22 more
TL;DR: In this paper, a metabolomic analysis of 163 serum and stool samples of a metabolic disease cohort was performed, and they identified glycoursodeoxycholic acid (GUDCA), glycine-conjugated bile acid produced from intestinal bacteria.
Journal ArticleDOI
Expression of the receptor of advanced glycation end-products (RAGE) and membranal location in peripheral blood mononuclear cells (PBMC) in obesity and insulin resistance.
Ruelas Cinco Edc,Ruíz Madrigal B,Domínguez Rosales Ja,Maldonado González M,De la Cruz Color L,Ramírez Meza Sm,Torres Baranda,Martínez López E,Hernández Nazará Zh +8 more
TL;DR: OB-IR subjects did not reflect significant differences in gene expression; however, correlations detected between sRAGE, biochemical parameters, and NRF2, besides the predominant RAGE distribution on the cell membrane in PBMC could be evidence of the early phase of the inflammatory cascade and the subsequent damage in specific tissues in subjects with OB-IR.
References
More filters
Journal ArticleDOI
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)
Han Cho,James Mu,Jason K. Kim,Jason K. Kim,Joanne L. Thorvaldsen,Qingwei Chu,E. Bryan Crenshaw,Klaus H. Kaestner,Marisa S. Bartolomei,Gerald I. Shulman,Gerald I. Shulman,Morris J. Birnbaum +11 more
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
Kathryn E. Wellen,Georgia Hatzivassiliou,Uma M. Sachdeva,Thi Bui,Justin R. Cross,Craig B. Thompson +5 more
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.