Glucose-Dependent Insulinotropic Polypeptide Enhances Adipocyte Development and Glucose Uptake in Part Through Akt Activation
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Background & aims In addition to its role as the primary mediator of the enteroinsular axis, glucose-dependent insulinotropic polypeptide (GIP) may play a critical role in the development of obesity. The purpose of these studies was to characterize the effects of GIP and its receptor (GIPR) in adipocyte development and signaling.Methods Effects of GIP and GIPR on differentiated 3T3-L1 cells were analyzed using Western blot analysis, Oil-Red-O staining, cyclic adenosine monophosphate radioimmunoassay, immunofluorescence microscopy, and glucose uptake measurements.Results To determine whether GIP and GIPR are important components in adipocyte development, the expression profile of GIPR during differentiation was examined. GIPR protein expression was enhanced during the differentiation process, and coincubation with its ligand GIP augmented the expression of aP2, a fat cell marker. Conversely, the suppression of GIPR expression by a specific short hairpin RNA attenuated Oil-Red-O staining and aP2 expression, suggesting that the GIPR may play a critical role in adipocyte development. To investigate specific signaling components that may mediate the effects of GIP, we analyzed Akt, glucose transporter-4, and glucose uptake, all of which are modulated by insulin in fat cells. Like insulin, GIP induced the activation of Akt in a concentration-dependent manner, promoted membrane glucose transporter-4 accumulation, and enhanced [(3)H]-2-deoxyglucose uptake.Conclusions These studies provide further evidence for an important physiologic role for GIP in lipid homeostasis and possibly in the pathogenesis of obesity. Furthermore, our data indicate that the GIPR might represent a suitable target for the treatment of obesity.
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Based on lipogenetic properties of GIP, insufficient insulin-potentiating effects in T2DM, and possible worsening effect, focus is on GLP-1 analogues/receptor agonists for T2DM treatment.
“However, based on the lipogenetic properties205, 206, 207 of GIP, insufficient insulin-potentiating effects in T2DM patients220, 336 and a possible worsening effect by GIP,337, 338 the focus is on GLP-1 analogues/receptor agonists for T2DM treatment.”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [206]
GIP-R expression increases with the differentiation of adipocytes.
“Furthermore, GIP-R expression increases with the differentiation of adipocytes [107].”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [107]
GIP facilitates increased glucose uptake, lipoprotein lipase activity and lipogenesis in isolated fat cells.
“Increased glucose uptake, lipoprotein lipase activity and lipogenesis (i.e., the re-esterification of free fatty acids (FFA) into TAG in vitro in isolated fat cells) are all facilitated by GIP [105,106,107].”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [107]
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- Authors
- Song, D. H., Getty–Kaushik, L., Tseng, E., Simon, J., Corkey, B. E., & Wolfe, M. M.
- Affiliations
- Boston University (US)
- Corresponding author
- Wolfe, M. Michael
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 133
- Issue
- 6
- Pages
- 1796-1805
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC2185546
- OpenAlex
- W1978898901
- Cited by
- 137
- References
- 51
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 11 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 8 · 2019: 8 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 11 · 2013: 2 · 2012: 15
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK053158, F32DK067812)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- glucose-dependent insulinotropic polypeptide, GIP receptor, adipogenesis, glucose uptake, Akt signaling, glucose transporter 4, 3T3-L1 cells, obesity, lipid homeostasis, enteroinsular axis, AP-2, shRNA knockdown
- MeSH terms
- Cell Differentiation, Cells, Cultured, Gastric Inhibitory Polypeptide, Glucose, Humans, Receptors, Gastrointestinal Hormone, Signal Transduction, Adipocytes, Insulin-Secreting Cells, Proto-Oncogene Proteins c-akt, Glucose Transporter Type 4
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