Journal ArticleDOI
What if Minkowski had been ageusic? An alternative angle on diabetes.
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TLDR
It is suggested that the phenomena of insulin resistance and hyperglycemia might be more readily understood if viewed in the context of underlying abnormalities of lipid metabolism.Abstract:
Despite decades of intensive investigation, the basic pathophysiological mechanisms responsible for the metabolic derangements associated with diabetes mellitus have remained elusive. Explored here is the possibility that traditional concepts in this area might have carried the wrong emphasis. It is suggested that the phenomena of insulin resistance and hyperglycemia might be more readily understood if viewed in the context of underlying abnormalities of lipid metabolism.read more
Citations
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Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.
Haiyan Xu,Glenn Barnes,Qing Yang,Guo Tan,Daseng Yang,Chieh J. Chou,Jason Sole,Andrew Nichols,Jeffrey S. Ross,Louis A. Tartaglia,Hong Chen +10 more
TL;DR: It is proposed that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue, and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance.
Journal ArticleDOI
Role of AMP-activated protein kinase in mechanism of metformin action
Gaochao Zhou,Robert W. Myers,Ying Li,Yuli Chen,Xiaolan Shen,Judy Fenyk-Melody,Margaret Wu,John Ventre,Thomas W. Doebber,Nobuharu Fujii,Nicolas Musi,Michael F. Hirshman,Laurie J. Goodyear,David E. Moller +13 more
TL;DR: It is reported that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed.
Journal ArticleDOI
Cellular mechanisms of insulin resistance
TL;DR: It is shown that commonly accepted models that attempt to explain the association of insulin resistance and obesity are incompatible with recent findings and an alternative model is proposed that appears to fit these and other available data.
Journal ArticleDOI
Reactive oxygen species have a causal role in multiple forms of insulin resistance.
TL;DR: A genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-α and the other with the glucocorticoid dexamethasone, suggests that reactive oxygen species levels are increased in both models, and increased ROS levels are an important trigger for insulin resistance in numerous settings.
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Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
TL;DR: A unifying hypothesis is proposed whereby hyperglycemia and FFA-induced activation of the nuclear factor-kappaB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases stress pathways plays a key role in causing late complications in type 1 and type 1 diabetes, along with insulin resistance and impaired insulin secretion in type 2 diabetes.
References
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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.
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Regulation of hepatic fatty acid oxidation and ketone body production.
J. D. McGarry,Daniel W. Foster +1 more
TL;DR: The role of Exogenous Fatly Acids in the Control of Ketogenesis and Applications of the Model are examined.
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Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid.
Leonard H Storlien,Arthur B. Jenkins,Donald J. Chisholm,Wendy S. Pascoe,Sue Khouri,Edward W. Kraegen +5 more
TL;DR: It is concluded that the particular fatty acids and the lipid environment in which they are presented in high-fat diets determine insulin sensitivity in rats and impaired insulin action in skeletal muscle relates to triglyceride accumulation, suggesting intracellular glucose–fatty acid cycle involvement.
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Measurement of Plasma Glucose, Free Fatty Acid, Lactate, and Insulin for 24 h in Patients With NIDDM
TL;DR: There are differences in substrate level between individuals with normal glucose tolerance and patients with NIDDM and differing degrees of glucose intolerance, unrelated to ambient insulin level, and these changes persist over 24 h.
Journal ArticleDOI
Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus
Nathalie Vionnet,Markus Stoffel,J. Takeda,K. Yasuda,Graeme I. Bell,Habib Zouali,Suzanne Lesage,Gilberto Velho,F. Iris,Ph. Passa,Philippe Froguel,David M. Cohen +11 more
TL;DR: The identification of a nonsense mutation in the gene encoding glucokinase and its linkage with early-onset diabetes in one family is reported, the first evidence implicating a mutation in a gene involved in glucose metabolism in the pathogenesis of NIDDM.