Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes
The challenges of achieving optimal glycemic control in type 2 diabetes highlight the need for new therapies. Inappropriately elevated endogenous glucose production (EGP) is the main source of hyperglycemia in type 2 diabetes. Because activation of central ATP-sensitive potassium (KATP) channels sup...
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| Format: | Online |
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American Diabetes Association
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001178/ |
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pubmed-50011782017-09-01 Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes Esterson, Yonah B. Carey, Michelle Boucai, Laura Goyal, Akankasha Raghavan, Pooja Zhang, Kehao Mehta, Deeksha Feng, Daorong Wu, Licheng Kehlenbrink, Sylvia Koppaka, Sudha Kishore, Preeti Hawkins, Meredith Metabolism The challenges of achieving optimal glycemic control in type 2 diabetes highlight the need for new therapies. Inappropriately elevated endogenous glucose production (EGP) is the main source of hyperglycemia in type 2 diabetes. Because activation of central ATP-sensitive potassium (KATP) channels suppresses EGP in nondiabetic rodents and humans, this study examined whether type 2 diabetic humans and rodents retain central regulation of EGP. The KATP channel activator diazoxide was administered in a randomized, placebo-controlled crossover design to eight type 2 diabetic subjects and seven age- and BMI-matched healthy control subjects. Comprehensive measures of glucose turnover and insulin sensitivity were performed during euglycemic pancreatic clamp studies following diazoxide and placebo administration. Complementary rodent clamp studies were performed in Zucker Diabetic Fatty rats. In type 2 diabetic subjects, extrapancreatic KATP channel activation with diazoxide under fixed hormonal conditions failed to suppress EGP, whereas matched control subjects demonstrated a 27% reduction in EGP (P = 0.002) with diazoxide. Diazoxide also failed to suppress EGP in diabetic rats. These results suggest that suppression of EGP by central KATP channel activation may be lost in type 2 diabetes. Restoration of central regulation of glucose metabolism could be a promising therapeutic target to reduce hyperglycemia in type 2 diabetes. American Diabetes Association 2016-09 2016-05-10 /pmc/articles/PMC5001178/ /pubmed/27207526 http://dx.doi.org/10.2337/db15-1465 Text en © 2016 by the American Diabetes Association. http://diabetesjournals.org/site/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://diabetesjournals.org/site/license. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Esterson, Yonah B. Carey, Michelle Boucai, Laura Goyal, Akankasha Raghavan, Pooja Zhang, Kehao Mehta, Deeksha Feng, Daorong Wu, Licheng Kehlenbrink, Sylvia Koppaka, Sudha Kishore, Preeti Hawkins, Meredith |
| spellingShingle |
Esterson, Yonah B. Carey, Michelle Boucai, Laura Goyal, Akankasha Raghavan, Pooja Zhang, Kehao Mehta, Deeksha Feng, Daorong Wu, Licheng Kehlenbrink, Sylvia Koppaka, Sudha Kishore, Preeti Hawkins, Meredith Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes |
| author_facet |
Esterson, Yonah B. Carey, Michelle Boucai, Laura Goyal, Akankasha Raghavan, Pooja Zhang, Kehao Mehta, Deeksha Feng, Daorong Wu, Licheng Kehlenbrink, Sylvia Koppaka, Sudha Kishore, Preeti Hawkins, Meredith |
| author_sort |
Esterson, Yonah B. |
| title |
Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes |
| title_short |
Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes |
| title_full |
Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes |
| title_fullStr |
Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes |
| title_full_unstemmed |
Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes |
| title_sort |
central regulation of glucose production may be impaired in type 2 diabetes |
| description |
The challenges of achieving optimal glycemic control in type 2 diabetes highlight the need for new therapies. Inappropriately elevated endogenous glucose production (EGP) is the main source of hyperglycemia in type 2 diabetes. Because activation of central ATP-sensitive potassium (KATP) channels suppresses EGP in nondiabetic rodents and humans, this study examined whether type 2 diabetic humans and rodents retain central regulation of EGP. The KATP channel activator diazoxide was administered in a randomized, placebo-controlled crossover design to eight type 2 diabetic subjects and seven age- and BMI-matched healthy control subjects. Comprehensive measures of glucose turnover and insulin sensitivity were performed during euglycemic pancreatic clamp studies following diazoxide and placebo administration. Complementary rodent clamp studies were performed in Zucker Diabetic Fatty rats. In type 2 diabetic subjects, extrapancreatic KATP channel activation with diazoxide under fixed hormonal conditions failed to suppress EGP, whereas matched control subjects demonstrated a 27% reduction in EGP (P = 0.002) with diazoxide. Diazoxide also failed to suppress EGP in diabetic rats. These results suggest that suppression of EGP by central KATP channel activation may be lost in type 2 diabetes. Restoration of central regulation of glucose metabolism could be a promising therapeutic target to reduce hyperglycemia in type 2 diabetes. |
| publisher |
American Diabetes Association |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001178/ |
| _version_ |
1613637348030939136 |