Role of non‐esterified fatty acids in the pathogenesis of Type 2 diabetes mellitus

Over 30 years after the original description of Randle’s cycle, the mechanisms by which elevated circulating non‐esterified fatty acids might be causally related to glucose intolerance in Type 2 diabetes mellitus remain uncertain. This review examines the evidence that elevated plasma NEFA can inhibit glucose‐stimulated insulin secretion by pancreatic beta‐cells and impair glucose‐ and insulin‐stimulated glucose disposal by peripheral tissues. Experimental evidence beginning to examine the mechanisms of these phenomena is discussed. © 1998 John Wiley & Sons, Ltd.