TY - JOUR
T1 - Central and peripheral administration of fibroblast growth factor 1 improves pancreatic islet insulin secretion in diabetic mouse models
AU - Tennant, Katherine G.
AU - Lindsley, Sarah R.
AU - Kirigiti, Melissa A.
AU - True, Cadence
AU - Kievit, Paul
N1 - Funding Information:
Acknowledgments. The authors thank their colleague, Dr. Charles Roberts (Oregon National Primate Research Center), for editorial assistance. Funding. This work was supported in part by the National Institutes of Health Office of the Director (grant P51OD01192 for operation of the Oregon National Primate Research Center) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK079194 to P.K.). Duality of Interest. P.K. receives research support from Novo Nordisk, Leidos Biomedical Inc., and Janssen Pharmaceuticals unrelated to the work presented in this article. No other potential conflicts of interest relevant to this article were reported. Author Contributions. K.G.T. conceived and designed the experiments, performed experiments, analyzed data, interpreted results of experiments, prepared figures, and drafted, edited, revised, and approved the final version of the manuscript. S.R.L. performed the c-Fos and metabolic cage and IHC experiments and analyzed c-Fos data. M.A.K. performed the c-Fos and IHC experiments and edited and revised the manuscript. C.T. interpreted results of experiments and edited and revised the manuscript. P.K. conceived and designed the experiments, analyzed data, interpreted results of experiments, and edited, revised, and approved the final version of the manuscript. P.K. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented as an oral abstract at the 100th Annual Meeting of the Endocrine Society, Chicago, IL, 17–20 March 2018.
Publisher Copyright:
© 2019 by the American Diabetes Association.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.2337/db18-1175
DO - 10.2337/db18-1175
M3 - Article
C2 - 31048370
AN - SCOPUS:85068538032
VL - 68
SP - 1462
EP - 1472
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -