The Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.

TitleThe Brain-to-Pancreatic Islet Neuronal Map Reveals Differential Glucose Regulation From Distinct Hypothalamic Regions.
Publication TypeJournal Article
Year of Publication2016
AuthorsRosario, W, Singh, I, Wautlet, A, Patterson, C, Flak, J, Becker, TC, Ali, A, Tamarina, N, Philipson, LH, Enquist, LW, Myers, MG, Rhodes, CJ
JournalDiabetes
Volume65
Issue9
Pagination2711-23
Date Published2016 Sep
ISSN1939-327X
Abstract

The brain influences glucose homeostasis, partly by supplemental control over insulin and glucagon secretion. Without this central regulation, diabetes and its complications can ensue. Yet, the neuronal network linking to pancreatic islets has never been fully mapped. Here, we refine this map using pseudorabies virus (PRV) retrograde tracing, indicating that the pancreatic islets are innervated by efferent circuits that emanate from the hypothalamus. We found that the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMN), and lateral hypothalamic area (LHA) significantly overlap PRV and the physiological glucose-sensing enzyme glucokinase. Then, experimentally lowering glucose sensing, specifically in the ARC, resulted in glucose intolerance due to deficient insulin secretion and no significant effect in the VMN, but in the LHA it resulted in a lowering of the glucose threshold that improved glucose tolerance and/or improved insulin sensitivity, with an exaggerated counter-regulatory response for glucagon secretion. No significant effect on insulin sensitivity or metabolic homeostasis was noted. Thus, these data reveal novel direct neuronal effects on pancreatic islets and also render a functional validation of the brain-to-islet neuronal map. They also demonstrate that distinct regions of the hypothalamus differentially control insulin and glucagon secretion, potentially in partnership to help maintain glucose homeostasis and guard against hypoglycemia.

DOI10.2337/db15-0629
Alternate JournalDiabetes
PubMed ID27207534
PubMed Central IDPMC5001176
Grant ListR01 DK099359 / DK / NIDDK NIH HHS / United States
R01 DK098853 / DK / NIDDK NIH HHS / United States
T32 DK087703 / DK / NIDDK NIH HHS / United States
P40 RR018604 / RR / NCRR NIH HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
P30 DK020595 / DK / NIDDK NIH HHS / United States
P60 DK020595 / DK / NIDDK NIH HHS / United States