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Effect of endogenous GLP-1 on insulin secretion in type 2 diabetes.

Salehi M, Aulinger B, Prigeon RL, D'Alessio DA - Diabetes (2010)

Bottom Line: However, Ex-9 also reduced the insulin response to intravenous glucose (25 +/- 5% vs. 26 +/- 7%; diabetic vs. nondiabetic subjects), when plasma GLP-1 levels were undetectable.Surprisingly, GLP-1 receptor signaling promotes glucose-stimulated insulin secretion independent of the mode of glucose entry.Based on rates of D-xylose absorption, GLP-1 receptor blockade did not affect gastric emptying of a solid meal.

View Article: PubMed Central - PubMed

Affiliation: University of Cincinnati, Department of Internal Medicine, Cincinnati, Ohio, USA. salehim@uc.edu

ABSTRACT

Objective: The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) account for up to 60% of postprandial insulin release in healthy people. Previous studies showed a reduced incretin effect in patients with type 2 diabetes but a robust response to exogenous GLP-1. The primary goal of this study was to determine whether endogenous GLP-1 regulates insulin secretion in type 2 diabetes.

Methods: Twelve patients with well-controlled type 2 diabetes and eight matched nondiabetic subjects consumed a breakfast meal containing D-xylose during fixed hyperglycemia at 5 mmol/l above fasting levels. Studies were repeated, once with infusion of the GLP-1 receptor antagonist, exendin-(9-39) (Ex-9), and once with saline.

Results: The relative increase in insulin secretion after meal ingestion was comparable in diabetic and nondiabetic groups (44 +/- 4% vs. 47 +/- 7%). Blocking the action of GLP-1 suppressed postprandial insulin secretion similarly in the diabetic and nondiabetic subjects (25 +/- 4% vs. 27 +/- 8%). However, Ex-9 also reduced the insulin response to intravenous glucose (25 +/- 5% vs. 26 +/- 7%; diabetic vs. nondiabetic subjects), when plasma GLP-1 levels were undetectable. The appearance of postprandial ingested d-xylose in the blood was not affected by Ex-9.

Conclusions: These findings indicate that in patients with well-controlled diabetes, the relative effects of enteral stimuli and endogenous GLP-1 to enhance insulin release are retained and comparable with those in nondiabetic subjects. Surprisingly, GLP-1 receptor signaling promotes glucose-stimulated insulin secretion independent of the mode of glucose entry. Based on rates of D-xylose absorption, GLP-1 receptor blockade did not affect gastric emptying of a solid meal.

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Related in: MedlinePlus

The contribution of GLP-1 to preprandial and postprandial insulin secretion. The percentage reduction of insulin secretion rates by Ex-9 is shown for the preprandial (60–90 min) and postprandial (95–270 min) periods in the nondiabetic (black bars) and diabetic (gray bars) groups. Data are presented as mean ± SEM.
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Figure 3: The contribution of GLP-1 to preprandial and postprandial insulin secretion. The percentage reduction of insulin secretion rates by Ex-9 is shown for the preprandial (60–90 min) and postprandial (95–270 min) periods in the nondiabetic (black bars) and diabetic (gray bars) groups. Data are presented as mean ± SEM.

Mentions: In both the diabetic and nondiabetic groups, β-cell secretion rose in response to intravenous glucose administration to a plateau from 60 to 90 min (Fig. 2, Table 2); preprandial insulin, C-peptide, and ISR were greater in the nondiabetic than the diabetic group (P < 0.05). Among the diabetic subjects, there were significant inverse correlations between the preprandial insulin secretory response and fasting glucose (r = −0.7, P < 0.01) and A1C (r = −0.8, P < 0.05). Compared with the study with saline infusion, GLP-1r blockade with Ex-9 caused a significant reduction of insulin secretion before meal ingestion (60–90 min), as indicated by significantly lower mean values of insulin, C-peptide, and ISR (Table 2). The GLP-1 effect on intravenous glucose–stimulated insulin secretion, taken as the percentage difference in mean ISR from 60 to 90 min with and without Ex-9, was 25 ± 5% in diabetic subjects and 26 ± 7% in the nondiabetic group (Fig. 3).


Effect of endogenous GLP-1 on insulin secretion in type 2 diabetes.

Salehi M, Aulinger B, Prigeon RL, D'Alessio DA - Diabetes (2010)

The contribution of GLP-1 to preprandial and postprandial insulin secretion. The percentage reduction of insulin secretion rates by Ex-9 is shown for the preprandial (60–90 min) and postprandial (95–270 min) periods in the nondiabetic (black bars) and diabetic (gray bars) groups. Data are presented as mean ± SEM.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874693&req=5

Figure 3: The contribution of GLP-1 to preprandial and postprandial insulin secretion. The percentage reduction of insulin secretion rates by Ex-9 is shown for the preprandial (60–90 min) and postprandial (95–270 min) periods in the nondiabetic (black bars) and diabetic (gray bars) groups. Data are presented as mean ± SEM.
Mentions: In both the diabetic and nondiabetic groups, β-cell secretion rose in response to intravenous glucose administration to a plateau from 60 to 90 min (Fig. 2, Table 2); preprandial insulin, C-peptide, and ISR were greater in the nondiabetic than the diabetic group (P < 0.05). Among the diabetic subjects, there were significant inverse correlations between the preprandial insulin secretory response and fasting glucose (r = −0.7, P < 0.01) and A1C (r = −0.8, P < 0.05). Compared with the study with saline infusion, GLP-1r blockade with Ex-9 caused a significant reduction of insulin secretion before meal ingestion (60–90 min), as indicated by significantly lower mean values of insulin, C-peptide, and ISR (Table 2). The GLP-1 effect on intravenous glucose–stimulated insulin secretion, taken as the percentage difference in mean ISR from 60 to 90 min with and without Ex-9, was 25 ± 5% in diabetic subjects and 26 ± 7% in the nondiabetic group (Fig. 3).

Bottom Line: However, Ex-9 also reduced the insulin response to intravenous glucose (25 +/- 5% vs. 26 +/- 7%; diabetic vs. nondiabetic subjects), when plasma GLP-1 levels were undetectable.Surprisingly, GLP-1 receptor signaling promotes glucose-stimulated insulin secretion independent of the mode of glucose entry.Based on rates of D-xylose absorption, GLP-1 receptor blockade did not affect gastric emptying of a solid meal.

View Article: PubMed Central - PubMed

Affiliation: University of Cincinnati, Department of Internal Medicine, Cincinnati, Ohio, USA. salehim@uc.edu

ABSTRACT

Objective: The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) account for up to 60% of postprandial insulin release in healthy people. Previous studies showed a reduced incretin effect in patients with type 2 diabetes but a robust response to exogenous GLP-1. The primary goal of this study was to determine whether endogenous GLP-1 regulates insulin secretion in type 2 diabetes.

Methods: Twelve patients with well-controlled type 2 diabetes and eight matched nondiabetic subjects consumed a breakfast meal containing D-xylose during fixed hyperglycemia at 5 mmol/l above fasting levels. Studies were repeated, once with infusion of the GLP-1 receptor antagonist, exendin-(9-39) (Ex-9), and once with saline.

Results: The relative increase in insulin secretion after meal ingestion was comparable in diabetic and nondiabetic groups (44 +/- 4% vs. 47 +/- 7%). Blocking the action of GLP-1 suppressed postprandial insulin secretion similarly in the diabetic and nondiabetic subjects (25 +/- 4% vs. 27 +/- 8%). However, Ex-9 also reduced the insulin response to intravenous glucose (25 +/- 5% vs. 26 +/- 7%; diabetic vs. nondiabetic subjects), when plasma GLP-1 levels were undetectable. The appearance of postprandial ingested d-xylose in the blood was not affected by Ex-9.

Conclusions: These findings indicate that in patients with well-controlled diabetes, the relative effects of enteral stimuli and endogenous GLP-1 to enhance insulin release are retained and comparable with those in nondiabetic subjects. Surprisingly, GLP-1 receptor signaling promotes glucose-stimulated insulin secretion independent of the mode of glucose entry. Based on rates of D-xylose absorption, GLP-1 receptor blockade did not affect gastric emptying of a solid meal.

Show MeSH
Related in: MedlinePlus