Analysis of paradoxical observations on the association between leptin and insulin resistance

Abstract

Obesity is commonly associated with the development of insulin resistance and diabetes in humans and rodents. Insulin resistance and diabetes are observed in lipoatrophic individuals or rodent models of lipoatrophy. Here we focus on the role of leptin, the product of the obesity (ob) gene, in the development of insulin resistance and diabetes associated with obesity and lipoatrophy. We review the reported effects of leptin on whole body glucose metabolism and compare and contrast these with direct effects on skeletal muscle, fat and liver. This summary of paradoxical observations on the effects of leptin on glucose homeostasis and the ability of leptin to induce or improve insulin resistance suggests that a complex interplay exists between direct peripheral and centrally mediated effects of the hormone. Evidence suggesting that leptin acts as a mediator of insulin release from pancreatic beta cells is reviewed. Finally, intracellular signaling mechanisms stimulated by both leptin and insulin are discussed, with potential points of cross-talk suggested.

Insulin resistance induces hyperleptinemia, cardiac contractile dysfunction but not cardiac leptin resistance in ventricular myocytes

“…21,22,26 Our present study indicated that insulin resistance contributes to hyperleptinemia associated with cardiac contractile dysfunctions; however, it may not necessarily lead to cardiac leptin resistance. Although our study sheds some light on the interaction of insulin resistance and hyperleptinemia on cardiovascular function under obesity, the pathogenesis of cardiac contractile dysfunction under obesity still deserves further study.…”

“…Leptin resistance and insulin resistance KK Hintz et al hyperleptinemia is closely associated with several metabolic risk factors related to insulin resistance in diabetes or obesity. 21,22 However, there is a considerable variability between leptin levels and body mass index, suggesting that genetic and environmental factors may regulate leptin levels. Results from our current study suggested that leptin levels are associated with insulin resistance or impaired insulin secretion.…”

Resistance to obesity in Lou/C rats prevents ageing-associated metabolic alterations

“…Although insulin sensitivity was measured in 22-month-old rats, Wistar rats probably developed insulin resistance at an earlier age. However, since hyperleptinaemia preceded hyperinsulinaemia, leptin could contribute to the development of insulin resistance [42].…”

Linkage of serum leptin levels in families with sleep apnea

“…Recent animal work, showing complex interactions between leptin and insulin signaling pathways, and their modification by obesity, underscores the complexity of this phenotype, and the close relationship between insulin and leptin resistances. 29 The peak on chromosome 3 is near the gene coding for glycogen synthase kinase 3 beta (GSK3B), a protein kinase that regulates numerous intracellular signaling pathways and is abundantly expressed in the brain where it may be involved in signal transduction. If replicated, this finding would suggest that leptin levels may be partly determined by genes involved in insulin signaling and nutrient regulation.…”