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Endocrinology. 2019 Nov 29. pii: bqz029. doi: 10.1210/endocr/bqz029. [Epub ahead of print]

Proglucagon-Derived Peptides, GIP and Dipeptidyl Peptidase-4-Mechanisms of Action in Adipose Tissue.

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From the Department of Medicine, Lunenfeld-Tanenbaum Research Institute, M.t Sinai Hospital, University of Toronto, Toronto ON, Canada.


Proglucagon-derived peptides (PGDPS) and related gut hormones exemplified by glucose-dependent insulintropic polypeptide (GIP) regulate energy disposal and storage, through actions on metabolically sensitive organs, including adipose tissue. The actions of glucagon, GLP-1, GLP-2, GIP, and their rate limiting enzyme dipeptidyl peptidase-4, include direct and indirect regulation of islet hormone secretion, food intake, body weight, all contributing to control of white and brown adipose tissue activity. Moreover agents mimicking actions of these peptides are in use for the therapy of metabolic disorders with disordered energy homeostasis, such as diabetes, obesity and intestinal failure. Here we highlight current concepts and mechanisms for direct and indirect actions of these peptides on adipose tissue depots. The available data highlights the importance of indirect peptide actions for control of adipose tissue biology, consistent with the very low level of endogenous peptide receptor expression within white and brown adipose tissue depots. Finally, we discuss limitations and challenges for the interpretation of available experimental observations, coupled to identification of enduring concepts supported by more robust evidence.


Diabetes; Fat; G protein coupled receptors; Inflammation; Obesity; Peptides


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