Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 3843-3852 |
| Number of pages | 9 |
| Journal | Endocrinology |
| Volume | 155 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2014 |
| MoE publication type | A1 Journal article-refereed |
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Overexpression of PPAR{\gamma} Specifically in Pancreatic {\beta}-Cells Exacerbates Obesity-Induced Glucose Intolerance, Reduces {\beta}-Cell Mass, and Alters Islet Lipid Metabolism in Male Mice. / Hogh, K-Lynn N.; Craig, Michael N.; Uy, Christopher E.; Nygren, Heli; Asadi, Ali; Speck, Madeline; Fraser, Jordie D.; Rudecki, Alexander P.; Baker, Robert K.; Oresic, Matej; Gray, Sarah L. (Corresponding Author).
In: Endocrinology, Vol. 155, No. 10, 2014, p. 3843-3852.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Overexpression of PPAR{\gamma} Specifically in Pancreatic {\beta}-Cells Exacerbates Obesity-Induced Glucose Intolerance, Reduces {\beta}-Cell Mass, and Alters Islet Lipid Metabolism in Male Mice
AU - Hogh, K-Lynn N.
AU - Craig, Michael N.
AU - Uy, Christopher E.
AU - Nygren, Heli
AU - Asadi, Ali
AU - Speck, Madeline
AU - Fraser, Jordie D.
AU - Rudecki, Alexander P.
AU - Baker, Robert K.
AU - Oresic, Matej
AU - Gray, Sarah L.
PY - 2014
Y1 - 2014
N2 - The contribution of peroxisomal proliferator-activated receptor (PPAR)-{\gamma} agonism in pancreatic {\beta}-cells to the antidiabetic actions of thiazolidinediones has not been clearly elucidated. Genetic models of pancreatic {\beta}-cell PPAR{\gamma} ablation have revealed a potential role for PPAR{\gamma} in {\beta}-cell expansion in obesity but a limited role in normal {\beta}-cell physiology. Here we overexpressed PPAR{\gamma}1 or PPAR{\gamma}2 specifically in pancreatic {\beta}-cells of mice subjected to high-fat feeding using an associated adenovirus ({\beta}-PPAR{\gamma}1-HFD and {\beta}-PPAR{\gamma}2-HFD mice). We show {\beta}-cell-specific PPAR{\gamma}1 or PPAR{\gamma}2 overexpression in diet-induced obese mice exacerbated obesity-induced glucose intolerance with decreased {\gamma}-cell mass, increased islet cell apoptosis, and decreased plasma insulin compared with obese control mice ({\beta}-eGFP-HFD mice). Analysis of islet lipid composition in {\beta}-PPAR{\gamma}2-HFD mice revealed no significant changes in islet triglyceride content and an increase in only one of eight ceramide species measured. Interestingly {\beta}-PPAR{\gamma}2-HFD islets had significantly lower levels of lysophosphatidylcholines, lipid species shown to enhance insulin secretion in {\gamma}-cells. Gene expression profiling revealed increased expression of uncoupling protein 2 and genes involved in fatty acid transport and {\beta}-oxidation. In summary, transgenic overexpression of PPAR{\gamma} in {\beta}-cells in diet-induced obesity negatively impacts whole-animal carbohydrate metabolism associated with altered islet lipid content, increased expression of {\beta}-oxidative genes, and reduced {\beta}-cell mass.
AB - The contribution of peroxisomal proliferator-activated receptor (PPAR)-{\gamma} agonism in pancreatic {\beta}-cells to the antidiabetic actions of thiazolidinediones has not been clearly elucidated. Genetic models of pancreatic {\beta}-cell PPAR{\gamma} ablation have revealed a potential role for PPAR{\gamma} in {\beta}-cell expansion in obesity but a limited role in normal {\beta}-cell physiology. Here we overexpressed PPAR{\gamma}1 or PPAR{\gamma}2 specifically in pancreatic {\beta}-cells of mice subjected to high-fat feeding using an associated adenovirus ({\beta}-PPAR{\gamma}1-HFD and {\beta}-PPAR{\gamma}2-HFD mice). We show {\beta}-cell-specific PPAR{\gamma}1 or PPAR{\gamma}2 overexpression in diet-induced obese mice exacerbated obesity-induced glucose intolerance with decreased {\gamma}-cell mass, increased islet cell apoptosis, and decreased plasma insulin compared with obese control mice ({\beta}-eGFP-HFD mice). Analysis of islet lipid composition in {\beta}-PPAR{\gamma}2-HFD mice revealed no significant changes in islet triglyceride content and an increase in only one of eight ceramide species measured. Interestingly {\beta}-PPAR{\gamma}2-HFD islets had significantly lower levels of lysophosphatidylcholines, lipid species shown to enhance insulin secretion in {\gamma}-cells. Gene expression profiling revealed increased expression of uncoupling protein 2 and genes involved in fatty acid transport and {\beta}-oxidation. In summary, transgenic overexpression of PPAR{\gamma} in {\beta}-cells in diet-induced obesity negatively impacts whole-animal carbohydrate metabolism associated with altered islet lipid content, increased expression of {\beta}-oxidative genes, and reduced {\beta}-cell mass.
U2 - 10.1210/en.2014-1076
DO - 10.1210/en.2014-1076
M3 - Article
VL - 155
SP - 3843
EP - 3852
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 10
ER -