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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1462-1472 |
| Number of pages | 11 |
| Journal | Diabetes |
| Volume | 68 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jan 1 2019 |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Central and peripheral administration of fibroblast growth factor 1 improves pancreatic islet insulin secretion in diabetic mouse models. / Tennant, Katherine G.; Lindsley, Sarah R.; Kirigiti, Melissa A.; True, Cadence; Kievit, Paul.
In: Diabetes, Vol. 68, No. 7, 01.01.2019, p. 1462-1472.Research output: Contribution to journal › Article
}
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
PY - 2019/1/1
Y1 - 2019/1/1
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
VL - 68
SP - 1462
EP - 1472
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -