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Effects of High Glucose Levels and Glycated Serum on GIP Responsiveness in the Pancreatic Beta Cell Line HIT-T15.

Puddu A, Sanguineti R, Montecucco F, Viviani GL - J Diabetes Res (2015)

Bottom Line: The results showed that incubation with GS alone altered intracellular GIP signaling and decreased insulin secretion as compared to CTR.GS in combination with HG reduced the expression of GIPR and PI3K and abrogated GIP-induced AKT phosphorylation and GIP-stimulated insulin secretion.In conclusion, we showed that treatment with GS is associated with the loss of the insulinotropic effect of GIP in hyperglycemic conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 16143 Genoa, Italy.

ABSTRACT
Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone produced in the gastrointestinal tract that stimulates glucose dependent insulin secretion. Impaired incretin response has been documented in diabetic patients and was mainly related to the inability of the pancreatic beta cells to secrete insulin in response to GIP. Advanced Glycation End Products (AGEs) have been shown to play an important role in pancreatic beta cell dysfunction. The aim of this study is to investigate whether the exposure to AGEs can induce GIP resistance in the pancreatic beta cell line HIT-T15. Cells were cultured for 5 days in low (CTR) or high glucose (HG) concentration in the presence of AGEs (GS) to evaluate the expression of GIP receptor (GIPR), the intracellular signaling activated by GIP, and secretion of insulin in response to GIP. The results showed that incubation with GS alone altered intracellular GIP signaling and decreased insulin secretion as compared to CTR. GS in combination with HG reduced the expression of GIPR and PI3K and abrogated GIP-induced AKT phosphorylation and GIP-stimulated insulin secretion. In conclusion, we showed that treatment with GS is associated with the loss of the insulinotropic effect of GIP in hyperglycemic conditions.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the effects of hyperglycaemia and AGEs on GIP responsiveness in the pancreatic beta cell line HIT-T15. Chronic hyperglycemia leads to formation and accumulation of AGEs; therefore the diabetic milieu may be represented as a hyper glycemic environment (HG) reached in AGEs (GS). Together, HG and GS contribute to damage pancreatic beta cell function: expression of GIPR is reduced, and its intracellular signaling is altered, leading to a reduced secretory response to GIP and potentially explaining the loss of GIP responsiveness in T2 diabetes.
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fig6: Schematic representation of the effects of hyperglycaemia and AGEs on GIP responsiveness in the pancreatic beta cell line HIT-T15. Chronic hyperglycemia leads to formation and accumulation of AGEs; therefore the diabetic milieu may be represented as a hyper glycemic environment (HG) reached in AGEs (GS). Together, HG and GS contribute to damage pancreatic beta cell function: expression of GIPR is reduced, and its intracellular signaling is altered, leading to a reduced secretory response to GIP and potentially explaining the loss of GIP responsiveness in T2 diabetes.

Mentions: These results suggest that the loss of GIP responsiveness might be due to the downregulation of its receptor. This condition was related to the deterioration of beta cell function due to the combined stimulation in the presence of HG and GS. These findings may contribute to explain the loss of GIP responsiveness in type 2 diabetes patients (Figure 6).


Effects of High Glucose Levels and Glycated Serum on GIP Responsiveness in the Pancreatic Beta Cell Line HIT-T15.

Puddu A, Sanguineti R, Montecucco F, Viviani GL - J Diabetes Res (2015)

Schematic representation of the effects of hyperglycaemia and AGEs on GIP responsiveness in the pancreatic beta cell line HIT-T15. Chronic hyperglycemia leads to formation and accumulation of AGEs; therefore the diabetic milieu may be represented as a hyper glycemic environment (HG) reached in AGEs (GS). Together, HG and GS contribute to damage pancreatic beta cell function: expression of GIPR is reduced, and its intracellular signaling is altered, leading to a reduced secretory response to GIP and potentially explaining the loss of GIP responsiveness in T2 diabetes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4499629&req=5

fig6: Schematic representation of the effects of hyperglycaemia and AGEs on GIP responsiveness in the pancreatic beta cell line HIT-T15. Chronic hyperglycemia leads to formation and accumulation of AGEs; therefore the diabetic milieu may be represented as a hyper glycemic environment (HG) reached in AGEs (GS). Together, HG and GS contribute to damage pancreatic beta cell function: expression of GIPR is reduced, and its intracellular signaling is altered, leading to a reduced secretory response to GIP and potentially explaining the loss of GIP responsiveness in T2 diabetes.
Mentions: These results suggest that the loss of GIP responsiveness might be due to the downregulation of its receptor. This condition was related to the deterioration of beta cell function due to the combined stimulation in the presence of HG and GS. These findings may contribute to explain the loss of GIP responsiveness in type 2 diabetes patients (Figure 6).

Bottom Line: The results showed that incubation with GS alone altered intracellular GIP signaling and decreased insulin secretion as compared to CTR.GS in combination with HG reduced the expression of GIPR and PI3K and abrogated GIP-induced AKT phosphorylation and GIP-stimulated insulin secretion.In conclusion, we showed that treatment with GS is associated with the loss of the insulinotropic effect of GIP in hyperglycemic conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 16143 Genoa, Italy.

ABSTRACT
Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone produced in the gastrointestinal tract that stimulates glucose dependent insulin secretion. Impaired incretin response has been documented in diabetic patients and was mainly related to the inability of the pancreatic beta cells to secrete insulin in response to GIP. Advanced Glycation End Products (AGEs) have been shown to play an important role in pancreatic beta cell dysfunction. The aim of this study is to investigate whether the exposure to AGEs can induce GIP resistance in the pancreatic beta cell line HIT-T15. Cells were cultured for 5 days in low (CTR) or high glucose (HG) concentration in the presence of AGEs (GS) to evaluate the expression of GIP receptor (GIPR), the intracellular signaling activated by GIP, and secretion of insulin in response to GIP. The results showed that incubation with GS alone altered intracellular GIP signaling and decreased insulin secretion as compared to CTR. GS in combination with HG reduced the expression of GIPR and PI3K and abrogated GIP-induced AKT phosphorylation and GIP-stimulated insulin secretion. In conclusion, we showed that treatment with GS is associated with the loss of the insulinotropic effect of GIP in hyperglycemic conditions.

No MeSH data available.


Related in: MedlinePlus