Central and Peripheral Administration of Fibroblast Growth Factor 1 Improves Pancreatic Islet Insulin Secretion in Diabetic Mouse Models.

Abstract:

:Fibroblast growth factor 1 (FGF1) has been shown to reverse hyperglycemia in diabetic rodent models through peripheral and central administration routes. Previous studies demonstrated that insulin is required for central and peripheral FGF1 metabolic improvements; however, it is unknown if FGF1 targets insulin secretion at the islet level. Here we show for the first time that FGF1 increases islet insulin secretion in diabetic mouse models. FGF1 was administered via a single intracerebroventricular or multiple subcutaneous injections to leptin receptor-deficient (db/db), diet-induced obese, and control mice; pancreatic islets were isolated 7 days later for analysis of insulin secretion. Central and peripheral FGF1 significantly lowered blood glucose in vivo and increased ex vivo islet insulin secretion from diabetic, but not control, mice. FGF1 injections to the cisterna magna mimicked intracerebroventricular outcomes, pointing to a novel therapeutic potential. Central effects of FGF1 appeared dependent on reductions in food intake, whereas peripheral FGF1 had acute actions on islet function prior to significant changes in food intake or blood glucose. Additionally, peripheral, but not central, FGF1 increased islet β-cell density, suggesting that peripheral FGF1 may induce long-term changes in islet structure and function that are not present with central treatment.

journal_name

Diabetes

journal_title

Diabetes

authors

Tennant KG,Lindsley SR,Kirigiti MA,True C,Kievit P

doi

10.2337/db18-1175

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

1462-1472

issue

7

eissn

0012-1797

issn

1939-327X

pii

db18-1175

journal_volume

68

pub_type

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