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
Next-Generation Personalized Medicine: Implementation of Variability Patterns for Overcoming Drug Resistance in Chronic Diseases
TL;DR: A three-phase platform for overcoming drug resistance is described: introducing irregularity for improving drug response; establishing a deep learning, closed-loop algorithm for generating a personalized pattern of irregularity; and upscaling the algorithm by implementing quantified personal variability patterns along with other individualized genetic and proteomic-based ways.
Journal ArticleDOI
Lycopene Improves Bone Quality and Regulates AGE/RAGE/NF-кB Signaling Pathway in High-Fat Diet-Induced Obese Mice
Bingke Xia,Ruyuan Zhu,Hao Zhang,Beibei Chen,Yage Liu,Xuanyin Dai,Zimengwei Ye,Dandan Zhao,Fangfang Mo,Sihua Gao,Xiangdong Wang,D. Bromme,Lili Wang,Xinxiang Wang,Dongwei Zhang +14 more
TL;DR: Lycopene consumption reduced body weight gain and improved blood glucose and lipid metabolism in HFD-induced obese mice and preserved bone biomechanical strength, material profiles, and microarchitecture in obese mice, suggesting that lycopenes consumption may be beneficial for the management of obesity-induced osteoporosis.
Journal ArticleDOI
The Insulin Receptor: An Important Target for the Development of Novel Medicines and Pesticides
TL;DR: This review is expected to provide useful information for a better understanding of human IR-related diseases, as well as to facilitate the development of novel small-molecule activators and inhibitors of the IR for use as medicines or pesticides.
Journal ArticleDOI
Distinct roles of systemic and local actions of insulin on pancreatic β-cells
TL;DR: Insulin plays distinct roles in β- cell survival and β-cell mass regulation through its local and systemic actions on β-cells, respectively.
Journal ArticleDOI
Oxidative stress and metabolic diseases: Relevance and therapeutic strategies
Muhammad Faisal Manzoor,Zaira Arif,Asifa Kabir,Iqra Ahmad Asim Mehmood,Danial Munir,Aqsa Razzaq,Anwar Ali,Gulden Goksen,Viorica Cosier,Nazir Ahmad,Murtaza Ali,Alexandru Rusu +11 more
TL;DR: A review of the most recent scientific developments in dietary OS, the consequence of metabolic disorders, and their most significant clinical manifestations (T2DM and atherosclerosis) will also emphasize the effects of dietary approaches in alleviating OS in MS.
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.