Limits...
The GLP-1 analogue exenatide improves hepatic and muscle insulin sensitivity in diabetic rats: tracer studies in the basal state and during hyperinsulinemic-euglycemic clamp.

Wu H, Sui C, Xu H, Xia F, Zhai H, Zhang H, Weng P, Han B, Du S, Lu Y - J Diabetes Res (2014)

Bottom Line: During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-(14)C-glucose.During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp.In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

View Article: PubMed Central - PubMed

Affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.

ABSTRACT

Objective: Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues.

Methods: Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-(3)H-glucose and U-(13)C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-(14)C-glucose.

Results: In the diabetic rats, exenatide reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no effect.

Conclusion: In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

Show MeSH

Related in: MedlinePlus

HGP and the disappearance rate of glucose (GRd) during the hyperinsulinemic-euglycemic clamp steady state. HGP following an overnight fast was higher (P < 0.01) in the D group rats than that in the D + E group rats. During clamp steady state, HGP was greater (P < 0.01) in the D group rats than that in the D + E group rats (a). In the basal state, the D + E group rats had a lower GRd than the D group rats (P < 0.01). The C + E group rats also had a lower GRd than the C group rats, but this was not significantly different (b). Under the clamp steady state, the GRd of the D group rats was lower than that of the C group rats (P < 0.05) and that of the C + E group rats (P < 0.01). The GRd of the D + E group rats was also significantly lower than that of the C group rats (P < 0.01) and that of the C + E group rats (P < 0.05). There was no significant difference found between the C group rats and the C + E group rats (P > 0.05) (b). *P < 0.01, #P < 0.05 compared with basal. βP < 0.01, αP < 0.05 compared with C group. σP < 0.01, γP < 0.05 compared with C + E group. §P < 0.01,  φP < 0.05 compared with D group.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4279913&req=5

fig5: HGP and the disappearance rate of glucose (GRd) during the hyperinsulinemic-euglycemic clamp steady state. HGP following an overnight fast was higher (P < 0.01) in the D group rats than that in the D + E group rats. During clamp steady state, HGP was greater (P < 0.01) in the D group rats than that in the D + E group rats (a). In the basal state, the D + E group rats had a lower GRd than the D group rats (P < 0.01). The C + E group rats also had a lower GRd than the C group rats, but this was not significantly different (b). Under the clamp steady state, the GRd of the D group rats was lower than that of the C group rats (P < 0.05) and that of the C + E group rats (P < 0.01). The GRd of the D + E group rats was also significantly lower than that of the C group rats (P < 0.01) and that of the C + E group rats (P < 0.05). There was no significant difference found between the C group rats and the C + E group rats (P > 0.05) (b). *P < 0.01, #P < 0.05 compared with basal. βP < 0.01, αP < 0.05 compared with C group. σP < 0.01, γP < 0.05 compared with C + E group. §P < 0.01,  φP < 0.05 compared with D group.

Mentions: Basal insulin concentrations were as follows: C, 12.84 ± 5.26 μIu/mL; C + E, 15.00 ± 5.55 μIu/mL; D, 29.09 ± 3.61 μIu/mL; and D + E, 18.86 ± 2.48 μIu/mL. Corresponding rates of appearance of glucose were as follows: C, 42.27 ± 10.56 μmol/kg/min; C + E, 35.11 ± 3.96 μmol/kg/min; D, 121.07 ± 16.55 μmol/kg/min; and D + E, 94.70 ± 13.46 μmol/kg/min. The D + E group rats had lower glucose appearance rates than the D group rats (P < 0.01), while it had still significantly higher than the C group rats (P < 0.01) and the C + E group rats (P < 0.01). The C + E group rats also had a lower glucose appearance rates than the C group rats, but no significant difference was found (Figure 5(b)).


The GLP-1 analogue exenatide improves hepatic and muscle insulin sensitivity in diabetic rats: tracer studies in the basal state and during hyperinsulinemic-euglycemic clamp.

Wu H, Sui C, Xu H, Xia F, Zhai H, Zhang H, Weng P, Han B, Du S, Lu Y - J Diabetes Res (2014)

HGP and the disappearance rate of glucose (GRd) during the hyperinsulinemic-euglycemic clamp steady state. HGP following an overnight fast was higher (P < 0.01) in the D group rats than that in the D + E group rats. During clamp steady state, HGP was greater (P < 0.01) in the D group rats than that in the D + E group rats (a). In the basal state, the D + E group rats had a lower GRd than the D group rats (P < 0.01). The C + E group rats also had a lower GRd than the C group rats, but this was not significantly different (b). Under the clamp steady state, the GRd of the D group rats was lower than that of the C group rats (P < 0.05) and that of the C + E group rats (P < 0.01). The GRd of the D + E group rats was also significantly lower than that of the C group rats (P < 0.01) and that of the C + E group rats (P < 0.05). There was no significant difference found between the C group rats and the C + E group rats (P > 0.05) (b). *P < 0.01, #P < 0.05 compared with basal. βP < 0.01, αP < 0.05 compared with C group. σP < 0.01, γP < 0.05 compared with C + E group. §P < 0.01,  φP < 0.05 compared with D group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4279913&req=5

fig5: HGP and the disappearance rate of glucose (GRd) during the hyperinsulinemic-euglycemic clamp steady state. HGP following an overnight fast was higher (P < 0.01) in the D group rats than that in the D + E group rats. During clamp steady state, HGP was greater (P < 0.01) in the D group rats than that in the D + E group rats (a). In the basal state, the D + E group rats had a lower GRd than the D group rats (P < 0.01). The C + E group rats also had a lower GRd than the C group rats, but this was not significantly different (b). Under the clamp steady state, the GRd of the D group rats was lower than that of the C group rats (P < 0.05) and that of the C + E group rats (P < 0.01). The GRd of the D + E group rats was also significantly lower than that of the C group rats (P < 0.01) and that of the C + E group rats (P < 0.05). There was no significant difference found between the C group rats and the C + E group rats (P > 0.05) (b). *P < 0.01, #P < 0.05 compared with basal. βP < 0.01, αP < 0.05 compared with C group. σP < 0.01, γP < 0.05 compared with C + E group. §P < 0.01,  φP < 0.05 compared with D group.
Mentions: Basal insulin concentrations were as follows: C, 12.84 ± 5.26 μIu/mL; C + E, 15.00 ± 5.55 μIu/mL; D, 29.09 ± 3.61 μIu/mL; and D + E, 18.86 ± 2.48 μIu/mL. Corresponding rates of appearance of glucose were as follows: C, 42.27 ± 10.56 μmol/kg/min; C + E, 35.11 ± 3.96 μmol/kg/min; D, 121.07 ± 16.55 μmol/kg/min; and D + E, 94.70 ± 13.46 μmol/kg/min. The D + E group rats had lower glucose appearance rates than the D group rats (P < 0.01), while it had still significantly higher than the C group rats (P < 0.01) and the C + E group rats (P < 0.01). The C + E group rats also had a lower glucose appearance rates than the C group rats, but no significant difference was found (Figure 5(b)).

Bottom Line: During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-(14)C-glucose.During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp.In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

View Article: PubMed Central - PubMed

Affiliation: Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.

ABSTRACT

Objective: Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues.

Methods: Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-(3)H-glucose and U-(13)C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-(14)C-glucose.

Results: In the diabetic rats, exenatide reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no effect.

Conclusion: In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

Show MeSH
Related in: MedlinePlus