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Physiol Behav. 2017 May 1;173:9-14. doi: 10.1016/j.physbeh.2017.01.038. Epub 2017 Jan 22.

Hindbrain DPP-IV inhibition improves glycemic control and promotes negative energy balance.

Author information

1
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
2
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: hayesmr@mail.med.upenn.edu.

Abstract

The beneficial glycemic and food intake-suppressive effects of glucagon-like peptide-1 (GLP-1) have made this neuroendocrine system a leading target for pharmacological approaches to the treatment of diabetes and obesity. One strategy to increase the activity of endogenous GLP-1 is to prevent the rapid degradation of the hormone by the enzyme dipeptidyl peptidase-IV (DPP-IV). However, despite the expression of both DPP-IV and GLP-1 in the brain, and the clear importance of central GLP-1 receptor (GLP-1R) signaling for glycemic and energy balance control, the metabolic effects of central inhibition of DPP-IV activity are unclear. To test whether hindbrain DPP-IV inhibition suppresses blood glucose, feeding, and body weight gain, the effects of 4th intracerebroventricular (ICV) administration of the FDA-approved DPP-IV inhibitor sitagliptin were evaluated. Results indicate that hindbrain delivery of sitagliptin improves glycemic control in a GLP-1R-dependent manner, suggesting that this effect is due at least in part to increased endogenous brainstem GLP-1 activity after sitagliptin administration. Furthermore, 4th ICV injection of sitagliptin reduced 24h body weight gain and energy intake, with a selective suppression of high-fat diet, but not chow, intake. These data reveal a novel role for hindbrain GLP-1R activation in glycemic control and also demonstrate that DPP-IV inhibition in the caudal brainstem promotes negative energy balance.

KEYWORDS:

Blood glucose; Body weight; Food intake; Januvia; Sitagliptin

PMID:
28119159
DOI:
10.1016/j.physbeh.2017.01.038
[Indexed for MEDLINE]

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