Hormonal
Chronically elevated plasma free fatty acid (FFA) levels cause insulin resistance in muscle and liver and impair insulin secretion in pancreatic beta-cells, a process termed lipotoxicity.
In Type 2 Diabetes, high levels of free fatty acids in the blood drive insulin resistance in muscles and the liver, and damage the pancreas's ability to make insulin. This 'lipotoxicity' is caused by fat cells failing to store fat properly, leading to fat accumulating in organs where it shouldn't be. Reducing these fatty acid levels (e.g., via medications like thiazolidinediones or lifestyle changes that improve fat storage capacity) can improve insulin sensitivity.
It is now recognized that chronically elevated plasma FFA concentrations cause insulin resistance in muscle and liver (1, 2, 28, 30, 31) and impair insulin secretion (32, 33).
Why this rating
The paper cites extensive human and animal studies, including euglycemic insulin clamps and MRI data.
Source
Role of the Adipocyte, Free Fatty Acids, and Ectopic Fat in Pathogenesis of Type 2 Diabetes Mellitus: Peroxisomal Proliferator-Activated Receptor Agonists Provide a Rational Therapeutic Approach
Harold Bays et al. · The Journal of Clinical Endocrinology & Metabolism · 2004
DOI 10.1210/jc.2003-030723
More from this paper
- Thiazolidinediones (PPAR-gamma agonists) improve insulin sensitivity and beta-cell function by enhancing adipocyte insulin sensitivity, inhibiting lipolysis, reducing plasma FFA, and redistributing fat away from visceral and hepatic depots to subcutaneous fat.Good
- Dysfunctional adipocytes in T2DM produce excessive insulin-resistant and inflammatory cytokines (e.g., resistin, TNF-alpha, IL-6, PAI-1) and secrete reduced amounts of insulin-sensitizing adipocytokines (e.g., adiponectin).Good
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