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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

Treatments with GS and HG altered insulin secretion. Relative levels of intracellular insulin content (a) and insulin released in the supernatants of HIT-T15 cells challenged for 2 hours in the presence of 4 mmol/L glucose alone (b) or 10 nmol GIP (c). Data are expressed as mean ± SE versus CTR (n = 3). ∗∗P < 0.01 and ∗∗∗P < 0.001 versus CTR.
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fig5: Treatments with GS and HG altered insulin secretion. Relative levels of intracellular insulin content (a) and insulin released in the supernatants of HIT-T15 cells challenged for 2 hours in the presence of 4 mmol/L glucose alone (b) or 10 nmol GIP (c). Data are expressed as mean ± SE versus CTR (n = 3). ∗∗P < 0.01 and ∗∗∗P < 0.001 versus CTR.

Mentions: To verify whether decreased expression of GIPR and altered intracellular signaling induced by GIP were associated with loss of beta cell function, we evaluated GIP-induced insulin secretion in HIT-T15 cells grown at low or high glucose levels in presence of GS. Under static incubation conditions in KRB buffer containing 4 mmol/L glucose, the rate of insulin secretion was significantly decreased in cells cultured at low glucose concentration with GS as compared to cells cultured with low glucose alone (CTR) (Figure 5(a)). Intracellular insulin content in HIT-T15 cells grown with GS alone was comparable to control cells but significantly decreased in cells cultured under hyperglycemic condition (Figure 5(b)). The rate of insulin secretion in response to 10 nmol/L GIP stimulation was significantly reduced in cells grown with HG in combination with GS (Figure 5(c)).


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)

Treatments with GS and HG altered insulin secretion. Relative levels of intracellular insulin content (a) and insulin released in the supernatants of HIT-T15 cells challenged for 2 hours in the presence of 4 mmol/L glucose alone (b) or 10 nmol GIP (c). Data are expressed as mean ± SE versus CTR (n = 3). ∗∗P < 0.01 and ∗∗∗P < 0.001 versus CTR.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Treatments with GS and HG altered insulin secretion. Relative levels of intracellular insulin content (a) and insulin released in the supernatants of HIT-T15 cells challenged for 2 hours in the presence of 4 mmol/L glucose alone (b) or 10 nmol GIP (c). Data are expressed as mean ± SE versus CTR (n = 3). ∗∗P < 0.01 and ∗∗∗P < 0.001 versus CTR.
Mentions: To verify whether decreased expression of GIPR and altered intracellular signaling induced by GIP were associated with loss of beta cell function, we evaluated GIP-induced insulin secretion in HIT-T15 cells grown at low or high glucose levels in presence of GS. Under static incubation conditions in KRB buffer containing 4 mmol/L glucose, the rate of insulin secretion was significantly decreased in cells cultured at low glucose concentration with GS as compared to cells cultured with low glucose alone (CTR) (Figure 5(a)). Intracellular insulin content in HIT-T15 cells grown with GS alone was comparable to control cells but significantly decreased in cells cultured under hyperglycemic condition (Figure 5(b)). The rate of insulin secretion in response to 10 nmol/L GIP stimulation was significantly reduced in cells grown with HG in combination with GS (Figure 5(c)).

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