A5008863193- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Liver Disease Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Peroxisome Proliferator-Activated Receptors
- Mitochondrial Function and Pathology
- Diet, Metabolism, and Disease
- Muscle metabolism and nutrition
- Lipid metabolism and biosynthesis
- RNA modifications and cancer
- Diabetes and associated disorders
- Metabolomics and Mass Spectrometry Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Advanced MRI Techniques and Applications
- Diabetes Management and Research
- Glycogen Storage Diseases and Myoclonus
- Regulation of Appetite and Obesity
- Cholesterol and Lipid Metabolism
- RNA and protein synthesis mechanisms
- Diabetes Treatment and Management
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- RNA Research and Splicing
Yale University
2015-2024
University of New Haven
2002-2021
Capital Region of Denmark
2021
Chapel Haven Schleifer Center
2021
Diabetes Research Center
2019
Milbank Memorial Fund
2012-2014
Howard Hughes Medical Institute
1998-2013
University of Southern California
2013
Kaiser Permanente
2013
Twin Cities Orthopedics
2011
Insulin resistance is a major factor in the pathogenesis of type 2 diabetes elderly. To investigate how insulin arises, we studied healthy, lean, elderly and young participants matched for lean body mass fat mass. Elderly study were markedly insulin-resistant as compared with controls, this was attributable to reduced insulin-stimulated muscle glucose metabolism. These changes associated increased accumulation liver tissue assessed by 1H nuclear magnetic resonance (NMR) spectroscopy,...
Recent studies have demonstrated that fatty acids induce insulin resistance in skeletal muscle by blocking activation of receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase). To examine the mechanism which mediate this effect, rats were infused with either a lipid emulsion (consisting mostly 18:2 acids) or glycerol. Intracellular C18:2 CoA increased time-dependent fashion, reaching an ∼6-fold elevation 5 h, whereas there was no change concentration any other...
To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min simultaneous 13C 31P nuclear magnetic resonance spectroscopy nine healthy subjects presence of low (0.18 +/- 0.02 mM [mean SEM]; control) or high (1.93 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic 400 pM) clamp conditions for 6 h. During initial 3.5 h rate...
To examine the mechanism by which free fatty acids (FFA) induce insulin resistance in human skeletal muscle, glycogen, glucose-6-phosphate, and intracellular glucose concentrations were measured using carbon-13 phosphorous-31 nuclear magnetic resonance spectroscopy seven healthy subjects before after a hyperinsulinemic-euglycemic clamp following five-hour infusion of either lipid/heparin or glycerol/heparin. IRS-1–associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was also...
To examine the mechanism by which free fatty acids (FFAs) induce insulin resistance in vivo, awake chronically catheterized rats underwent a hyperinsulinemic-euglycemic clamp with or without 5-h preinfusion of lipid/heparin to raise plasma FFA concentrations. Increased FFAs resulted as reflected approximately 35% reduction glucose infusion rate (P < 0.05 vs. control). The was associated 40-50% 13C nuclear magnetic resonance (NMR)-determined rates muscle glycogen synthesis 0.01...
We examined the hypothesis that insulin resistance in skeletal muscle promotes development of atherogenic dyslipidemia, associated with metabolic syndrome, by altering distribution pattern postprandial energy storage. Following ingestion two high carbohydrate mixed meals, net glycogen synthesis was reduced approximately 60% young, lean, insulin-resistant subjects compared a similar cohort age-weight-body mass index-activity-matched, insulin-sensitive, control subjects. In contrast, hepatic...
Insulin resistance in the offspring of parents with non-insulin-dependent diabetes mellitus (NIDDM) is best predictor development disease and probably plays an important part its pathogenesis. We studied mechanism degree to which exercise training improves insulin sensitivity these subjects.
Lipodystrophy is a rare disorder that characterized by selective loss of subcutaneous and visceral fat associated with hypertriglyceridemia, hepatomegaly, disordered glucose metabolism. It has recently been shown chronic leptin treatment ameliorates these abnormalities. Here we show improves insulin-stimulated hepatic peripheral metabolism in severely insulin-resistant lipodystrophic patients. This improvement insulin action was marked reduction muscle triglyceride content. These data...
Insulin resistance, a major factor in the pathogenesis of type 2 diabetes mellitus, is due mostly to decreased stimulation glycogen synthesis muscle by insulin. The primary rate-controlling step responsible for decrease not known, although hexokinase activity and glucose transport have been implicated.
We examined the effect of three months rosiglitazone treatment (4 mg b.i.d.) on whole-body insulin sensitivity and in vivo peripheral adipocyte as assessed by glycerol release microdialysis from subcutaneous fat during a two-step (20 120 mU · m−2 min−1) hyperinsulinemic-euglycemic clamp nine type 2 diabetic subjects. In addition, effects liver muscle triglyceride content were 1H-nuclear magnetic resonance spectroscopy. Rosiglitazone resulted 68% (P < 0.002) 20% 0.016) improvement...
Lipodystrophy is a rare disorder that characterized by selective loss of subcutaneous and visceral fat associated with hypertriglyceridemia, hepatomegaly, disordered glucose metabolism. It has recently been shown chronic leptin treatment ameliorates these abnormalities. Here we show improves insulin-stimulated hepatic peripheral metabolism in severely insulin-resistant lipodystrophic patients. This improvement insulin action was marked reduction muscle triglyceride content. These data...
The circulating level of the inflammatory cytokine interleukin (IL)-6 is elevated in various insulin-resistant states including type 2 diabetes, obesity, cancer, and HIV-associated lipodystrophy. To determine role IL-6 development insulin resistance, we examined effects treatment on whole-body action glucose metabolism vivo during hyperinsulinemic-euglycemic clamps awake mice. Pretreatment blunted insulin's ability to suppress hepatic production insulin-stimulated receptor substrate...
Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations fat metabolism. Recent studies have suggested that local accumulation metabolites inside skeletal muscle activate serine kinase cascade involving protein C–θ (PKC-θ), leading defects insulin signaling glucose transport muscle. To test this hypothesis, we examined whether mice with inactivation PKC-θ are protected from fat-induced Skeletal hepatic action as assessed during...
Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations fat metabolism. Recent studies have suggested that local accumulation metabolites inside skeletal muscle activate serine kinase cascade involving protein C–θ (PKC-θ), leading defects insulin signaling glucose transport muscle. To test this hypothesis, we examined whether mice with inactivation PKC-θ are protected from fat-induced Skeletal hepatic action as assessed during...
Nonalcoholic fatty liver disease (NAFLD) is a major contributing factor to hepatic insulin resistance in type 2 diabetes. Diacylglycerol acyltransferase (Dgat), of which there are two isoforms (Dgat1 and Dgat2), catalyzes the final step triglyceride synthesis. We evaluated metabolic impact pharmacological reduction DGAT1 -2 expression fat using antisense oligonucleotides (ASOs) rats with diet-induced NAFLD. Dgat1 Dgat2 ASO treatment selectively reduced DGAT2 mRNA levels fat, but only...
<h3>Importance</h3>Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain insulin resistance. Fructose ingestion produces smaller increases circulating satiety hormones compared with glucose ingestion, central administration provokes feeding rodents, whereas centrally administered promotes satiety.<h3>Objective</h3>To study neurophysiological factors that might underlie associations between...
To determine whether plasma lactate can be a significant fuel for human brain energy metabolism, infusions of [3- 13 C]lactate and 1 H- C polarization transfer spectroscopy were used to detect the entry utilization lactate. During 2 h infusion study, incorporation in amino acid pools glutamate glutamine measured with 5 min time resolution. With concentration ([Lac] P ) being 0.8–2.8 mmol/L range, tissue B was assessed as well fractional contribution metabolism (CMRlac). From relationship...
Acetyl-CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation. To examine the impact ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation and total expenditure Acc2(-/-) WT control mice fed either regular or high-fat diets. determine insulin action vivo, also insulin-stimulated liver muscle glucose metabolism during hyperinsulinemic-euglycemic clamp diet. Contrary to previous studies that have suggested increased might result lower...