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Glucose-dependent insulinotropic polypeptide signaling in pancreatic β-cells and adipocytes.

McIntosh CH, Widenmaier S, Kim SJ - J Diabetes Investig (2012)

Bottom Line: Recent studies have shown that inhibition of the kinase apoptosis signal-regulating kinase 1 (ASK1) by GIP plays a key role in reducing mitochondria-induced apoptosis in β-cells through protein kinase B (PKB)-mediated pathways, and that GIP-induced post-translational modification of voltage- dependent K(+) (Kv) channels also contributes to its prosurvival role.Through regulation of gene expression, GIP tips the balance between pro- and anti-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family towards β-cell survival.GIP also plays important roles in the differentiation of pre-adipocytes to adipocytes, and in the regulation of lipoprotein lipase expression and lipogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Physiological Sciences and the Diabetes Research Group, Life Sciences Institute University of British Columbia, Vancouver, BC, Canada.

ABSTRACT
Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin to be identified. In addition to stimulating insulin secretion, GIP plays regulatory roles in the maintenance, growth and survival of pancreatic islets, as well as impacting on adipocyte function. The current review focuses on the intracellular signaling pathways by which GIP contributes to the regulation of β-cell secretion and survival, and adipocyte differentiation and lipogenesis. Studies on signaling underlying the insulinotropic actions of the incretin hormones have largely been carried out with glucagon-like peptide-1. They have provided evidence for contributions by both protein kinase A (PKA) and exchange protein directly activated by cyclic adenosine monophosphate (EPAC2), and their probable role in GIP signaling is discussed. Recent studies have shown that inhibition of the kinase apoptosis signal-regulating kinase 1 (ASK1) by GIP plays a key role in reducing mitochondria-induced apoptosis in β-cells through protein kinase B (PKB)-mediated pathways, and that GIP-induced post-translational modification of voltage- dependent K(+) (Kv) channels also contributes to its prosurvival role. Through regulation of gene expression, GIP tips the balance between pro- and anti-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family towards β-cell survival. GIP also plays important roles in the differentiation of pre-adipocytes to adipocytes, and in the regulation of lipoprotein lipase expression and lipogenesis. These events involve interactions between GIP, insulin and resistin signaling pathways. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00196.x, 2012).

No MeSH data available.


Related in: MedlinePlus

 Glucose‐dependent insulinotropic polypeptide receptor (GIPR) and peroxisome proliferator‐activated receptor (PPAR)γ protein expression levels in adipose tissue depots from lean and obese Vancouver Diabetic Fatty (VDF) Zucker rats. Tissue was collected from 18‐week‐old rats and western blot analyses were carried out, with quantification by densitometry (n = 4–6 rats). Significance was tested using analysis of variance (anova) with Newman–Keuls post‐hoc test. **P < 0.05 vs lean control group. IBAT, interscapular brown adipose tissue.
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f3:  Glucose‐dependent insulinotropic polypeptide receptor (GIPR) and peroxisome proliferator‐activated receptor (PPAR)γ protein expression levels in adipose tissue depots from lean and obese Vancouver Diabetic Fatty (VDF) Zucker rats. Tissue was collected from 18‐week‐old rats and western blot analyses were carried out, with quantification by densitometry (n = 4–6 rats). Significance was tested using analysis of variance (anova) with Newman–Keuls post‐hoc test. **P < 0.05 vs lean control group. IBAT, interscapular brown adipose tissue.

Mentions: Evidence has been presented for the involvement of both PPARα109,110 and PPARγ111 in the regulation of rodent β‐cell GIPR expression, and further studies are required to clarify whether there are cell‐selective differences in regulation. Additionally, in earlier studies, it was shown that the GIPR is downregulated in β‐cells of obese rodent models of diabetes109,110,112, but in studies on Vancouver Diabetic Fatty (VDF) Zucker rats, we recently found that, compared with lean controls, GIPR and PPARγ protein levels were increased in epididymal and retroperitoneal fat pads, decreased in the perirenal fat depot and unchanged in other fat deposits (Figure 3). In contrast, GIPR expression in subcutaneous adipose tissue from human obese females was reported to be lower than in lean control subjects113. However, these results are difficult to compare, because of the different fat depots studied. Additionally, the sensitivity of GIPR expression to the prevailing insulin concentration, the level of adipose tissue insulin resistance and the glycemic status of the subjects/animals could all contribute significantly to the level of GIPR expression.


Glucose-dependent insulinotropic polypeptide signaling in pancreatic β-cells and adipocytes.

McIntosh CH, Widenmaier S, Kim SJ - J Diabetes Investig (2012)

 Glucose‐dependent insulinotropic polypeptide receptor (GIPR) and peroxisome proliferator‐activated receptor (PPAR)γ protein expression levels in adipose tissue depots from lean and obese Vancouver Diabetic Fatty (VDF) Zucker rats. Tissue was collected from 18‐week‐old rats and western blot analyses were carried out, with quantification by densitometry (n = 4–6 rats). Significance was tested using analysis of variance (anova) with Newman–Keuls post‐hoc test. **P < 0.05 vs lean control group. IBAT, interscapular brown adipose tissue.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4020726&req=5

f3:  Glucose‐dependent insulinotropic polypeptide receptor (GIPR) and peroxisome proliferator‐activated receptor (PPAR)γ protein expression levels in adipose tissue depots from lean and obese Vancouver Diabetic Fatty (VDF) Zucker rats. Tissue was collected from 18‐week‐old rats and western blot analyses were carried out, with quantification by densitometry (n = 4–6 rats). Significance was tested using analysis of variance (anova) with Newman–Keuls post‐hoc test. **P < 0.05 vs lean control group. IBAT, interscapular brown adipose tissue.
Mentions: Evidence has been presented for the involvement of both PPARα109,110 and PPARγ111 in the regulation of rodent β‐cell GIPR expression, and further studies are required to clarify whether there are cell‐selective differences in regulation. Additionally, in earlier studies, it was shown that the GIPR is downregulated in β‐cells of obese rodent models of diabetes109,110,112, but in studies on Vancouver Diabetic Fatty (VDF) Zucker rats, we recently found that, compared with lean controls, GIPR and PPARγ protein levels were increased in epididymal and retroperitoneal fat pads, decreased in the perirenal fat depot and unchanged in other fat deposits (Figure 3). In contrast, GIPR expression in subcutaneous adipose tissue from human obese females was reported to be lower than in lean control subjects113. However, these results are difficult to compare, because of the different fat depots studied. Additionally, the sensitivity of GIPR expression to the prevailing insulin concentration, the level of adipose tissue insulin resistance and the glycemic status of the subjects/animals could all contribute significantly to the level of GIPR expression.

Bottom Line: Recent studies have shown that inhibition of the kinase apoptosis signal-regulating kinase 1 (ASK1) by GIP plays a key role in reducing mitochondria-induced apoptosis in β-cells through protein kinase B (PKB)-mediated pathways, and that GIP-induced post-translational modification of voltage- dependent K(+) (Kv) channels also contributes to its prosurvival role.Through regulation of gene expression, GIP tips the balance between pro- and anti-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family towards β-cell survival.GIP also plays important roles in the differentiation of pre-adipocytes to adipocytes, and in the regulation of lipoprotein lipase expression and lipogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Physiological Sciences and the Diabetes Research Group, Life Sciences Institute University of British Columbia, Vancouver, BC, Canada.

ABSTRACT
Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin to be identified. In addition to stimulating insulin secretion, GIP plays regulatory roles in the maintenance, growth and survival of pancreatic islets, as well as impacting on adipocyte function. The current review focuses on the intracellular signaling pathways by which GIP contributes to the regulation of β-cell secretion and survival, and adipocyte differentiation and lipogenesis. Studies on signaling underlying the insulinotropic actions of the incretin hormones have largely been carried out with glucagon-like peptide-1. They have provided evidence for contributions by both protein kinase A (PKA) and exchange protein directly activated by cyclic adenosine monophosphate (EPAC2), and their probable role in GIP signaling is discussed. Recent studies have shown that inhibition of the kinase apoptosis signal-regulating kinase 1 (ASK1) by GIP plays a key role in reducing mitochondria-induced apoptosis in β-cells through protein kinase B (PKB)-mediated pathways, and that GIP-induced post-translational modification of voltage- dependent K(+) (Kv) channels also contributes to its prosurvival role. Through regulation of gene expression, GIP tips the balance between pro- and anti-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family towards β-cell survival. GIP also plays important roles in the differentiation of pre-adipocytes to adipocytes, and in the regulation of lipoprotein lipase expression and lipogenesis. These events involve interactions between GIP, insulin and resistin signaling pathways. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00196.x, 2012).

No MeSH data available.


Related in: MedlinePlus