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Cell Rep. 2016 Apr 5;15(1):36-44. doi: 10.1016/j.celrep.2016.02.088. Epub 2016 Mar 24.

Leptin Controls Parasympathetic Wiring of the Pancreas during Embryonic Life.

Author information

1
The Saban Research Institute, Developmental Neuroscience Program, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
2
INSERM, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille 59045, France.
3
The Saban Research Institute, Developmental Neuroscience Program, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA; INSERM, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille 59045, France. Electronic address: sbouret@chla.usc.edu.

Abstract

The autonomic nervous system plays a critical role in glucose metabolism through both its sympathetic and parasympathetic branches, but the mechanisms that underlie the development of the autonomic innervation of the pancreas remain poorly understood. Here, we report that cholinergic innervation of pancreatic islets develops during mid-gestation under the influence of leptin. Leptin-deficient mice display a greater cholinergic innervation of pancreatic islets beginning in embryonic life, and this increase persists into adulthood. Remarkably, a single intracerebroventricular injection of leptin in embryos caused a permanent reduction in parasympathetic innervation of pancreatic β cells and long-term impairments in glucose homeostasis. These developmental effects of leptin involve a direct inhibitory effect on the outgrowth of preganglionic axons from the hindbrain. These studies reveal an unanticipated regulatory role of leptin on the parasympathetic nervous system during embryonic development and may have important implications for our understanding of the early mechanisms that contribute to diabetes.

PMID:
27052164
PMCID:
PMC4982372
DOI:
10.1016/j.celrep.2016.02.088
[Indexed for MEDLINE]
Free PMC Article

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