Hepatic Glucose Sensing Is Impaired, but Can Be Normalized, in People With Impaired Fasting Glucose
| Autor: | Anna Kerege, Bryan C. Bergman, Leigh Perreault, Samantha Bacon, Kristine Færch |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty endocrine system diseases Endocrinology Diabetes and Metabolism Clinical Biochemistry Endogeny Fructose Hot Topics in Translational Endocrinology Biochemistry Prediabetic State chemistry.chemical_compound Endocrinology Internal medicine Diabetes mellitus Glucose Intolerance Humans Medicine Glucose tolerance test medicine.diagnostic_test business.industry Glucokinase Biochemistry (medical) nutritional and metabolic diseases Fasting Glucose Tolerance Test Glucose clamp technique Impaired fasting glucose medicine.disease Somatostatin Diabetes Mellitus Type 2 Liver chemistry Hyperglycemia Glucose Clamp Technique Female business hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 99:E1154-E1162 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2013-3248 |
| Popis: | Abnormal endogenous glucose production (EGP) is a characteristic feature in people with impaired fasting glucose (IFG). We sought to determine whether impaired hepatic glucose sensing contributes to abnormal EGP in IFG and whether it could be experimentally restored.Glucose production (rate of appearance; Ra) and flux (glucose cycling) were assessed during a hyperglycemic-euinsulinemic somatostatin clamp with an infusion of [6,6-(2)H2-]glucose and [2-(2)H]glucose before and after enhanced hepatic glucokinase activity via an infusion of low-dose fructose in people with IFG and normal glucose tolerance (NGT).During euglycemia, neither endogenous glucose production [(6,6-(2)H2)-glucose Ra; P = 0.53] or total glucose output (TGO; [2-(2)H]-glucose Ra; P = .12) was different between groups, but glucose cycling ([2-(2)H]glucose Ra to [6,6-(2)H2-]glucose Ra; a surrogate measure of hepatic glucokinase activity in the postabsorptive state) was lower in IFG than NGT (P = .04). Hyperglycemia suppressed EGP more in NGT than IFG (P.01 for absolute or relative suppression, NGT vs IFG), whereas TGO decreased similarly in both groups (P = .77). The addition of fructose completely suppressed EGP in IFG (P.01) and tended to do the same to TGO (P = .01; no such changes in NGT, P = .39-.55). Glucose cycling (which reflects glucose-6-phosphatase activity during glucose infusion) was similar in IFG and NGT (P = .51) during hyperglycemia and was unchanged and comparable between groups with the addition of fructose (P = .24).In summary, glucose sensing is impaired in IFG but can be experimentally restored with low-dose fructose. Glucokinase activation may prove to be a novel strategy for the prevention of diabetes in this high-risk group. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|