The cellular mechanisms by which insulin promotes glucose uptake and metabolism in healthy subjects will be examined utilizing: (a) insulin/hyperglycemic clamp; (b) indirect calorimetry; (c) forearm catheterization; (d) several novel isotopic methodologies recently developed in our laboratory; (e) muscle biopsy. These techniques will allow in vivo quantitation in man of the following parameters: glucose transport and phosphorylation, glucose oxidation, glycolysis, glycogen synthesis, muscle enzyme activity (glycogen synthase and pyruvate dehydrogenase), and hepatic glucose production. Similar measurements will be performed in diabetic and obese patients t delineate the specific intracellular disturbances which are responsible for the insulin resistance (both peripheral and hepatic) in these two common clinical disorders. The contribution of hyperglycemia per se (""""""""glucose toxicity"""""""") t the observed defects in insulin action and insulin secretion in non-insulin dependent diabetes mellitus will be explored in detail. We also shall examine the effects of chronic hyperinsulinemia on the oxidative and non-oxidative pathways of glucose disposal.
| Shannon, Chris; Merovci, Aurora; Xiong, Juan et al. (2018) Effect of Chronic Hyperglycemia on Glucose Metabolism in Subjects With Normal Glucose Tolerance. Diabetes 67:2507-2517 |
| DeFronzo, Ralph A (2017) Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes Obes Metab 19:1353-1362 |
| Abdul-Ghani, Muhammad; DeFronzo, Ralph A; Del Prato, Stefano et al. (2017) Cardiovascular Disease and Type 2 Diabetes: Has the Dawn of a New Era Arrived? Diabetes Care 40:813-820 |
| Abdul-Ghani, Muhammad; DeFronzo, Ralph A (2017) Is It Time to Change the Type 2 Diabetes Treatment Paradigm? Yes! GLP-1 RAs Should Replace Metformin in the Type 2 Diabetes Algorithm. Diabetes Care 40:1121-1127 |
| Merovci, Aurora; Abdul-Ghani, Muhammad; Mari, Andrea et al. (2016) Effect of Dapagliflozin With and Without Acipimox on Insulin Sensitivity and Insulin Secretion in T2DM Males. J Clin Endocrinol Metab 101:1249-56 |
| DeFronzo, Ralph A (2016) The EMPA-REG study: What has it told us? A diabetologist's perspective. J Diabetes Complications 30:1-2 |
| Daniele, Giuseppe; Xiong, Juan; Solis-Herrera, Carolina et al. (2016) Dapagliflozin Enhances Fat Oxidation and Ketone Production in Patients With Type 2 Diabetes. Diabetes Care 39:2036-2041 |
| Abdul-Ghani, Muhammad; Del Prato, Stefano; Chilton, Robert et al. (2016) SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study. Diabetes Care 39:717-25 |
| DeFronzo, Ralph A; Ferrannini, Ele; Groop, Leif et al. (2015) Type 2 diabetes mellitus. Nat Rev Dis Primers 1:15019 |
| Abdul-Ghani, Muhammad A; Norton, Luke; DeFronzo, Ralph A (2015) Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus. Am J Physiol Renal Physiol 309:F889-900 |
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