Gerald I. Shulman
Yale University
EndocrinologyInsulin resistanceInsulinDiabetes mellitusBiology
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Publications 598
#1Ikki Sakuma (Yale University)
#2Masataka Yokoyama (Chiba University)H-Index: 1
Last. Tomoaki Tanaka (Chiba University)H-Index: 29
view all 7 authors...
#1Yuichi Nozaki (Yale University)H-Index: 1
#2Max C. Petersen (Yale University)H-Index: 11
Last. Varman T. Samuel (Yale University)H-Index: 48
view all 15 authors...
Multiple insulin-regulated enzymes participate in hepatic glycogen synthesis, and the rate-controlling step responsible for insulin stimulation of glycogen synthesis is unknown. We demonstrate that glucokinase (GCK)-mediated glucose phosphorylation is the rate-controlling step in insulin-stimulated hepatic glycogen synthesis in vivo, by use of the somatostatin pancreatic clamp technique using [13C6]glucose with metabolic control analysis (MCA) in three rat models: 1) regular chow (RC)-fed male r...
1 CitationsSource
#1L. Bilet (UM: Maastricht University)H-Index: 6
#2Esther Phielix (UM: Maastricht University)H-Index: 20
Last. Kenneth Meijer (UM: Maastricht University)H-Index: 31
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AIMS/HYPOTHESIS: Physical inactivity, low mitochondrial function, increased intramyocellular lipid (IMCL) deposition and reduced insulin sensitivity are common denominators of chronic metabolic disorders, like obesity and type 2 diabetes. Yet, whether low mitochondrial function predisposes to insulin resistance in humans is still unknown. METHODS: Here we investigated, in an intervention study, whether muscle with low mitochondrial oxidative capacity, induced by one-legged physical inactivity, w...
#1Panu K. Luukkonen (Yale University)H-Index: 1
#2Sylvie Dufour (Yale University)H-Index: 16
Last. Hannele Yki-Järvinen (UH: University of Helsinki)H-Index: 101
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Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects receiv...
#1Rachel J. PerryH-Index: 18
#2Kun LyuH-Index: 1
Last. Gerald I. ShulmanH-Index: 144
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Meal ingestion increases body temperature in multiple species, an effect that is blunted by obesity. However, the mechanisms responsible for these phenomena remain incompletely understood. Here we show that refeeding increases plasma leptin concentrations approximately 8-fold in 48-hour-fasted lean rats, and this normalization of plasma leptin concentrations stimulates adrenomedullary catecholamine secretion. Increased adrenal medulla-derived plasma catecholamines were necessary and sufficient t...
#1Rachel J. Perry (Yale University)H-Index: 18
#2Dongyan Zhang (Yale University)H-Index: 30
Last. Sylvie Dufour (Yale University)H-Index: 16
view all 20 authors...
Although it is well-established that reductions in the ratio of insulin to glucagon in the portal vein have a major role in the dysregulation of hepatic glucose metabolism in type-2 diabetes1–3, the mechanisms by which glucagon affects hepatic glucose production and mitochondrial oxidation are poorly understood. Here we show that glucagon stimulates hepatic gluconeogenesis by increasing the activity of hepatic adipose triglyceride lipase, intrahepatic lipolysis, hepatic acetyl-CoA content and py...
1 CitationsSource
#1Elena TarabraH-Index: 1
#2Jessica NouwsH-Index: 4
Last. Sonia CaprioH-Index: 65
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Severe obesity (SO) affects about 6% of youth in US, augmenting the risks for cardiovascular disease and Type 2 diabetes.Herein, we obtained paired omental (omVAT) and abdominal subcutaneous (SAT) adipose tissue biopsies from obese girls with SO, undergoing sleeve gastrectomy (SG), to test whether differences in cellular and transcriptomic profiles between omVAT and SAT depots affect insulin sensitivity differentially. Following weight loss, these analyses were repeated in a subgroup of subjects...
1 CitationsSource
#1Sampada Chande (Yale University)H-Index: 1
#2Daniel Caballero (Yale University)H-Index: 3
Last. Nati Hernando (UZH: University of Zurich)H-Index: 30
view all 15 authors...
Low blood phosphate (Pi) reduces muscle function in hypophosphatemic disorders. Which Pi transporters are required and whether hormonal changes due to hypophosphatemia contribute to muscle function is unknown. To address these questions we generated a series of conditional knockout mice lacking one or both house-keeping Pi transporters Pit1 and Pit2 in skeletal muscle (sm), using the postnatally expressed human skeletal actin-cre. Simultaneous conditional deletion of both transporters caused ske...
#1Panjamaporn Sangwung (Cardiovascular Institute of the South)
#2Kitt Falk Petersen (Yale University)H-Index: 59
Last. Joshua W. Knowles (Cardiovascular Institute of the South)H-Index: 42
view all 4 authors...
Insulin resistance, IR, is fundamental to the development type 2 diabetes (T2D) and is present in most prediabetic (preDM) individuals. IR has both heritable and environmental determinants centered on energy storage and metabolism. Recent insights from human genetic studies, coupled with comprehensive in vivo and ex vivo metabolic studies in humans and rodents have highlighted the critical role of reduced mitochondrial function as a predisposing condition for ectopic lipid deposition and IR. The...
#1Naim Alkhouri (University of Texas at Austin)H-Index: 28
#1Naim Alkhouri (University of Texas at Austin)H-Index: 2
Last. Gerald I. Shulman (Yale University)H-Index: 144
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ABSTRACTIntroduction: De novo lipogenesis (DNL) plays a major role in fatty acid metabolism and contributes significantly to triglyceride accumulation within the hepatocytes in patients with nonalc...
2 CitationsSource