Associate Professor, Nutrition and Endocrinology & Metabolism
UNC Gillings School of Global Public Health
Cancer Cell Biology
Area of Interest
Eric Klett, MD, a practicing endocrinologist, is an associate professor of Medicine and Nutrition whose research interest is in the role of dietary fatty acid and intra-pancreatic beta-cell fatty acid metabolism on glucose-stimulated insulin secretion (GSIS). Insulin secretion is a complex process initiated by nutrient secretagogues, including glucose and fatty acids. GSIS is augmented by saturated long-chain fatty acids, but is impaired by ω-6 polyunsaturated fatty acids (PUFA). Glucose and fatty acids are essential to GSIS, though the exact molecular mechanism by which specific fatty acids alter GSIS remains unclear.
Dr. Klett has examined the role of one of the rate-limiting enzymes in glycerolipid synthesis on beta-cell function, acyl-CoA synthetase (ACSL). Specifically, exposing beta-cells to ω-6 PUFAs (arachidonate or linoleate) not only impairs GSIS, but also reduces ACSL isoform-4 (ACSL4) mRNA and protein expression. Further, reducing ACSL4 specific activity decreases GSIS. The reduction in insulin secretion is due to the accumulation of unesterified epoxyeicosatrienoic acids (EETs). The hypothesis that ACSL4 plays a key role in eicosanoid metabolism has significant implications in all disease processes that involve eicosanoid metabolism, including diabetes, cardiovascular disease, and cancer.