How does leptin restore euglycemia in insulin-deficient diabetes?
Douglas Oberlin, Christoph Buettner
Douglas Oberlin, Christoph Buettner
Published January 23, 2017
Citation Information: J Clin Invest. 2017;127(2):450-453. https://doi.org/10.1172/JCI91880.
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Commentary

How does leptin restore euglycemia in insulin-deficient diabetes?

Abstract

Insulin replacement is the cornerstone of type 1 diabetes (T1D) treatment; however, glycemic control remains a challenge. Leptin has been shown to effectively restore euglycemia in rodent models of T1D; however, the mechanism or mechanisms by which leptin exerts glycemic control are unclear. In this issue of the JCI, Perry and colleagues provide evidence that suppression of lipolysis is a key facet of leptin-mediated restoration of euglycemia. However, more work remains to be done to fully understand the antidiabetic mechanisms of leptin.

Authors

Douglas Oberlin, Christoph Buettner

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Figure 1

Model proposed by Perry et al. in this issue to explain the antidiabetic effects of leptin.

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Model proposed by Perry et al. in this issue to explain the antidiabetic...
Leptin restrains the activity of the HPA axis in T1D, reducing circulating corticosterone, which lowers lipolysis in adipose tissue. As of yet it remains unclear in what tissue and cell type GCs exert these lipolytic effects. Restrained lipolysis results in lower NEFAs and glycerol delivery to the liver, reducing gluconeogenesis and ketogenesis and thereby reversing hyperglycemia and DKA. PEPCK, phosphoenolpyruvate carboxykinase; G3P, glyceraldehyde 3-phosphate; HSL, hormone-sensitive lipase; PC, pyruvate carboxylase; βox, β oxidation.