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
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...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2014-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2014/524517 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849307964702195712 |
|---|---|
| author | Hui Wu Chunhua Sui Hui Xu Fangzhen Xia Hualing Zhai Huixin Zhang Pan Weng Bing Han Sichun Du Yingli Lu |
| author_facet | Hui Wu Chunhua Sui Hui Xu Fangzhen Xia Hualing Zhai Huixin Zhang Pan Weng Bing Han Sichun Du Yingli Lu |
| author_sort | Hui Wu |
| collection | DOAJ |
| description | 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 3-3H-glucose and U-13C-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-14C-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. |
| format | Article |
| id | doaj-art-1f460fad78ee4c3895b45fe732e7710c |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-1f460fad78ee4c3895b45fe732e7710c2025-08-20T03:54:36ZengWileyJournal of Diabetes Research2314-67452314-67532014-01-01201410.1155/2014/524517524517The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic ClampHui Wu0Chunhua Sui1Hui Xu2Fangzhen Xia3Hualing Zhai4Huixin Zhang5Pan Weng6Bing Han7Sichun Du8Yingli Lu9Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaInstitute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, ChinaObjective. 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 3-3H-glucose and U-13C-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-14C-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.http://dx.doi.org/10.1155/2014/524517 |
| spellingShingle | Hui Wu Chunhua Sui Hui Xu Fangzhen Xia Hualing Zhai Huixin Zhang Pan Weng Bing Han Sichun Du Yingli Lu 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 Journal of Diabetes Research |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | glp 1 analogue exenatide improves hepatic and muscle insulin sensitivity in diabetic rats tracer studies in the basal state and during hyperinsulinemic euglycemic clamp |
| url | http://dx.doi.org/10.1155/2014/524517 |
| work_keys_str_mv | AT huiwu theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT chunhuasui theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT huixu theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT fangzhenxia theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT hualingzhai theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT huixinzhang theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT panweng theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT binghan theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT sichundu theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT yinglilu theglp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT huiwu glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT chunhuasui glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT huixu glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT fangzhenxia glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT hualingzhai glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT huixinzhang glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT panweng glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT binghan glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT sichundu glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp AT yinglilu glp1analogueexenatideimproveshepaticandmuscleinsulinsensitivityindiabeticratstracerstudiesinthebasalstateandduringhyperinsulinemiceuglycemicclamp |