@article{gupta_physiologic_2010,
	title = {Physiologic and {Pharmacologic} {Modulation} of {Glucose}-{Dependent} {Insulinotropic} {Polypeptide} ({GIP}) {Receptor} {Expression} in β-{Cells} by {Peroxisome} {Proliferator}–{Activated} {Receptor} ({PPAR})-γ {Signaling}},
	volume = {59},
	issn = {0012-1797},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874705/},
	doi = {10.2337/db09-1655},
	abstract = {OBJECTIVE
We previously showed that peroxisome proliferator–activated receptor (PPAR)-γ in β-cells regulates pdx-1 transcription through a functional PPAR response element (PPRE). Gene Bank blast for a homologous nucleotide sequence revealed the same PPRE within the rat glucose-dependent insulinotropic polypeptide receptor (GIP-R) promoter sequence. We investigated the role of PPARγ in GIP-R transcription.

RESEARCH DESIGN AND METHODS
Chromatin immunoprecipitation assay, siRNA, and luciferase gene transcription assay in INS-1 cells were performed. Islet GIP-R expression and immunohistochemistry studies were performed in pancreas-specific PPARγ knockout mice (PANC PPARγ−/−), normoglycemic 60\% pancreatectomy rats (Px), normoglycemic and hyperglycemic Zucker fatty (ZF) rats, and mouse islets incubated with troglitazone.

RESULTS
In vitro studies of INS-1 cells confirmed that PPAR-γ binds to the putative PPRE sequence and regulates GIP-R transcription. In vivo verification was shown by a 70\% reduction in GIP-R protein expression in islets from PANC PPARγ−/− mice and a twofold increase in islets of 14-day post-60\% Px Sprague-Dawley rats that hyperexpress β-cell PPARγ. Thiazolidinedione activation (72 h) of this pathway in normal mouse islets caused a threefold increase of GIP-R protein and a doubling of insulin secretion to 16.7 mmol/l glucose/10 nmol/l GIP. Islets from obese normoglycemic ZF rats had twofold increased PPARγ and GIP-R protein levels versus lean rats, with both lowered by two-thirds in ZF rats made hyperglycemic by 60\% Px.

CONCLUSIONS
Our studies have shown physiologic and pharmacologic regulation of GIP-R expression in β-cells by PPARγ signaling. Also disruption of this signaling pathway may account for the lowered β-cell GIP-R expression and resulting GIP resistance in type 2 diabetes.},
	number = {6},
	urldate = {2025-07-21},
	journal = {Diabetes},
	author = {Gupta, Dhananjay and Peshavaria, Mina and Monga, Navjot and Jetton, Thomas L. and Leahy, Jack L.},
	month = jun,
	year = {2010},
	pages = {1445--1450},
}

{"_id":"bF4FN3DvSMGCeQbWF","bibbaseid":"gupta-peshavaria-monga-jetton-leahy-physiologicandpharmacologicmodulationofglucosedependentinsulinotropicpolypeptidegipreceptorexpressionincellsbyperoxisomeproliferatoractivatedreceptorpparsignaling-2010","author_short":["Gupta, D.","Peshavaria, M.","Monga, N.","Jetton, T. L.","Leahy, J. L."],"bibdata":{"bibtype":"article","type":"article","title":"Physiologic and Pharmacologic Modulation of Glucose-Dependent Insulinotropic Polypeptide (GIP) Receptor Expression in β-Cells by Peroxisome Proliferator–Activated Receptor (PPAR)-γ Signaling","volume":"59","issn":"0012-1797","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874705/","doi":"10.2337/db09-1655","abstract":"OBJECTIVE We previously showed that peroxisome proliferator–activated receptor (PPAR)-γ in β-cells regulates pdx-1 transcription through a functional PPAR response element (PPRE). Gene Bank blast for a homologous nucleotide sequence revealed the same PPRE within the rat glucose-dependent insulinotropic polypeptide receptor (GIP-R) promoter sequence. We investigated the role of PPARγ in GIP-R transcription. RESEARCH DESIGN AND METHODS Chromatin immunoprecipitation assay, siRNA, and luciferase gene transcription assay in INS-1 cells were performed. Islet GIP-R expression and immunohistochemistry studies were performed in pancreas-specific PPARγ knockout mice (PANC PPARγ−/−), normoglycemic 60% pancreatectomy rats (Px), normoglycemic and hyperglycemic Zucker fatty (ZF) rats, and mouse islets incubated with troglitazone. RESULTS In vitro studies of INS-1 cells confirmed that PPAR-γ binds to the putative PPRE sequence and regulates GIP-R transcription. In vivo verification was shown by a 70% reduction in GIP-R protein expression in islets from PANC PPARγ−/− mice and a twofold increase in islets of 14-day post-60% Px Sprague-Dawley rats that hyperexpress β-cell PPARγ. Thiazolidinedione activation (72 h) of this pathway in normal mouse islets caused a threefold increase of GIP-R protein and a doubling of insulin secretion to 16.7 mmol/l glucose/10 nmol/l GIP. Islets from obese normoglycemic ZF rats had twofold increased PPARγ and GIP-R protein levels versus lean rats, with both lowered by two-thirds in ZF rats made hyperglycemic by 60% Px. CONCLUSIONS Our studies have shown physiologic and pharmacologic regulation of GIP-R expression in β-cells by PPARγ signaling. Also disruption of this signaling pathway may account for the lowered β-cell GIP-R expression and resulting GIP resistance in type 2 diabetes.","number":"6","urldate":"2025-07-21","journal":"Diabetes","author":[{"propositions":[],"lastnames":["Gupta"],"firstnames":["Dhananjay"],"suffixes":[]},{"propositions":[],"lastnames":["Peshavaria"],"firstnames":["Mina"],"suffixes":[]},{"propositions":[],"lastnames":["Monga"],"firstnames":["Navjot"],"suffixes":[]},{"propositions":[],"lastnames":["Jetton"],"firstnames":["Thomas","L."],"suffixes":[]},{"propositions":[],"lastnames":["Leahy"],"firstnames":["Jack","L."],"suffixes":[]}],"month":"June","year":"2010","pages":"1445–1450","bibtex":"@article{gupta_physiologic_2010,\n\ttitle = {Physiologic and {Pharmacologic} {Modulation} of {Glucose}-{Dependent} {Insulinotropic} {Polypeptide} ({GIP}) {Receptor} {Expression} in β-{Cells} by {Peroxisome} {Proliferator}–{Activated} {Receptor} ({PPAR})-γ {Signaling}},\n\tvolume = {59},\n\tissn = {0012-1797},\n\turl = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874705/},\n\tdoi = {10.2337/db09-1655},\n\tabstract = {OBJECTIVE\nWe previously showed that peroxisome proliferator–activated receptor (PPAR)-γ in β-cells regulates pdx-1 transcription through a functional PPAR response element (PPRE). Gene Bank blast for a homologous nucleotide sequence revealed the same PPRE within the rat glucose-dependent insulinotropic polypeptide receptor (GIP-R) promoter sequence. We investigated the role of PPARγ in GIP-R transcription.\n\nRESEARCH DESIGN AND METHODS\nChromatin immunoprecipitation assay, siRNA, and luciferase gene transcription assay in INS-1 cells were performed. Islet GIP-R expression and immunohistochemistry studies were performed in pancreas-specific PPARγ knockout mice (PANC PPARγ−/−), normoglycemic 60\\% pancreatectomy rats (Px), normoglycemic and hyperglycemic Zucker fatty (ZF) rats, and mouse islets incubated with troglitazone.\n\nRESULTS\nIn vitro studies of INS-1 cells confirmed that PPAR-γ binds to the putative PPRE sequence and regulates GIP-R transcription. In vivo verification was shown by a 70\\% reduction in GIP-R protein expression in islets from PANC PPARγ−/− mice and a twofold increase in islets of 14-day post-60\\% Px Sprague-Dawley rats that hyperexpress β-cell PPARγ. Thiazolidinedione activation (72 h) of this pathway in normal mouse islets caused a threefold increase of GIP-R protein and a doubling of insulin secretion to 16.7 mmol/l glucose/10 nmol/l GIP. Islets from obese normoglycemic ZF rats had twofold increased PPARγ and GIP-R protein levels versus lean rats, with both lowered by two-thirds in ZF rats made hyperglycemic by 60\\% Px.\n\nCONCLUSIONS\nOur studies have shown physiologic and pharmacologic regulation of GIP-R expression in β-cells by PPARγ signaling. Also disruption of this signaling pathway may account for the lowered β-cell GIP-R expression and resulting GIP resistance in type 2 diabetes.},\n\tnumber = {6},\n\turldate = {2025-07-21},\n\tjournal = {Diabetes},\n\tauthor = {Gupta, Dhananjay and Peshavaria, Mina and Monga, Navjot and Jetton, Thomas L. and Leahy, Jack L.},\n\tmonth = jun,\n\tyear = {2010},\n\tpages = {1445--1450},\n}\n\n\n\n\n\n\n\n\n\n\n\n","author_short":["Gupta, D.","Peshavaria, M.","Monga, N.","Jetton, T. L.","Leahy, J. L."],"key":"gupta_physiologic_2010","id":"gupta_physiologic_2010","bibbaseid":"gupta-peshavaria-monga-jetton-leahy-physiologicandpharmacologicmodulationofglucosedependentinsulinotropicpolypeptidegipreceptorexpressionincellsbyperoxisomeproliferatoractivatedreceptorpparsignaling-2010","role":"author","urls":{"Paper":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874705/"},"metadata":{"authorlinks":{}},"downloads":0,"html":""},"bibtype":"article","biburl":"https://bibbase.org/zotero/ArthurLee1999","dataSources":["PS7iNi9NSaRnsipEv"],"keywords":[],"search_terms":["physiologic","pharmacologic","modulation","glucose","dependent","insulinotropic","polypeptide","gip","receptor","expression","cells","peroxisome","proliferator","activated","receptor","ppar","signaling","gupta","peshavaria","monga","jetton","leahy"],"title":"Physiologic and Pharmacologic Modulation of Glucose-Dependent Insulinotropic Polypeptide (GIP) Receptor Expression in β-Cells by Peroxisome Proliferator–Activated Receptor (PPAR)-γ Signaling","year":2010}