Gerald I. Shulman

Hepatic Glycogen Metabolism in Type 1 Diabetes After (2008)

Martin G. Bischof, Elisabeth Bernroider, Martin Krssak, Michael Krebs, Harald Stingl, ...

We tested the impact of long-term near normoglycemia (HbA 1c <7 % for>1 year) on glycogen metabolism in seven type 1 diabetic and seven matched nondiabetic subjects after a mixed meal. Glycemic...

A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice (2008)

David B. Savage, Lanmin Zhai, Balasubramanian Ravikumar, Cheol Soo Choi, Johanna E. Snaar, Amanda C. McGuire, ...

BackgroundStored glycogen is an important source of energy for skeletal muscle. Human genetic disorders primarily affecting skeletal muscle glycogen turnover are well-recognised, but rare. We...

Decreased Insulin-Stimulated ATP Synthesis and Phosphate Transport in Muscle of Insulin-Resistant Offspring of Type 2 Diabetic Parents (2005)

Kitt F. Petersen, Sylvie Dufour, Gerald I. Shulman

Background Insulin resistance is the best predictor for the development of type 2 diabetes. Recent studies have shown that young, lean, insulin-resistant (IR) offspring of parents with type 2...

Assessment of mitochondrial energy coupling in vivo by 13C/31P NMR

Jucker, Beat M., Dufour, Sylvie, Ren, Jianming, Cao, Xueying, Previs, Stephen F., Underhill, Brian, ...

The recently cloned uncoupling protein homolog UCP3 is expressed primarily in muscle and therefore may play a significant role in the regulation of energy expenditure and body weight. However,...

Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR

Shen, Jun, Petersen, Kitt F., Behar, Kevin L., Brown, Peter, Nixon, Terrence W., Mason, Graeme F., ...

Recent 13C NMR studies in rat models have shown that the glutamate/glutamine cycle is highly active in the cerebral cortex and is coupled to incremental glucose oxidation in an ≈1:1 stoichiometry....

Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance

Zabolotny, Janice M., Kim, Young-Bum, Peroni, Odile D., Kim, Jason K., Pani, Michael A., Boss, Olivier, ...

Previous reports indicate that the expression and/or activity of the protein-tyrosine phosphatase (PTP) LAR are increased in insulin-responsive tissues of obese, insulin-resistant humans and rodents,...

Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance

Kim, Jason K., Fillmore, Jonathan J., Chen, Yan, Yu, Chunli, Moore, Irene K., Pypaert, Marc, ...

Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to...

Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice

Klaman, Lori D., Boss, Olivier, Peroni, Odile D., Kim, Jason K., Martino, Jennifer L., Zabolotny, Janice M., ...

Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To...

AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation

Zong, Haihong, Ren, Jian Ming, Young, Lawrence H., Pypaert, Marc, Mu, James, Birnbaum, Morris J., ...

Mitochondrial biogenesis is a critical adaptation to chronic energy deprivation, yet the signaling mechanisms responsible for this response are poorly understood. To examine the role of AMP-activated...

Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes

Hundal, Ripudaman S., Petersen, Kitt F., Mayerson, Adam B., Randhawa, Pritpal S., Inzucchi, Silvio, Shoelson, Steven E., ...

Recent studies have implicated fatty acid-dependent activation of the serine kinase IKKβ, which plays a key role in tissue inflammation, in the pathogenesis of insulin resistance. High doses of...

Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy

Petersen, Kitt Falk, Oral, Elif Arioglu, Dufour, Sylvie, Befroy, Douglas, Ariyan, Charlotte, Yu, Chunli, ...

Lipodystrophy is a rare disorder that is characterized by selective loss of subcutaneous and visceral fat and is associated with hypertriglyceridemia, hepatomegaly, and disordered glucose metabolism....

Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways

Rui, Liangyou, Aguirre, Vincent, Kim, Jason K., Shulman, Gerald I., Lee, Anna, Corbould, Anne, ...

Serine/threonine phosphorylation of IRS-1 might inhibit insulin signaling, but the relevant phosphorylation sites are difficult to identify in cultured cells and to validate in isolated tissues....

Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance

Yang, Chunmei, Coker, Kenneth J., Kim, Jason K., Mora, Silvia, Thurmond, Debbie C., Davis, Ann C., ...

To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4–knockout mice. Homozygotic disruption...

Prevention of fat-induced insulin resistance by salicylate

Kim, Jason K., Kim, Yoon-Jung, Fillmore, Jonathan J., Chen, Yan, Moore, Irene, Lee, Jongsoon, ...

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation of a serine kinase cascade involving IKK-β. To test this hypothesis, we first...

Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle

Lebon, Vincent, Dufour, Sylvie, Petersen, Kitt Falk, Ren, Jianming, Jucker, Beat M., Slezak, Lori A., ...

The mechanism underlying the regulation of basal metabolic rate by thyroid hormone remains unclear. Although it has been suggested that thyroid hormone might uncouple substrate oxidation from ATP...

Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle

Kim, Jason K., Gimeno, Ruth E., Higashimori, Takamasa, Kim, Hyo-Jeong, Choi, Hyejeong, Punreddy, Sandhya, ...

Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid...

Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4

Kim, Jason K., Zisman, Ariel, Fillmore, Jonathan J., Peroni, Odile D., Kotani, Ko, Perret, Pascale, ...

Using cre/loxP gene targeting, transgenic mice with muscle-specific inactivation of the GLUT4 gene (muscle GLUT4 KO) were generated and shown to develop a diabetes phenotype. To determine the...

Glucose Disposal during Insulinopenia in Somatostatin-Treated Dogs: THE ROLES OF GLUCOSE AND GLUCAGON

Shulman, Gerald I., Liljenquist, John E., Williams, Phillip E., Lacy, William W., Cherrington, Alan D.

The first aim of this study was to determine whether the plasma glucose level can regulate hepatic glucose balance in vivo independent of its effects on insulin and glucagon secretion. To accomplish...

Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice

Gavrilova, Oksana, Marcus-Samuels, Bernice, Graham, David, Kim, Jason K., Shulman, Gerald I., Castle, Arthur L., ...

In lipoatrophic diabetes, a lack of fat is associated with insulin resistance and hyperglycemia. This is in striking contrast to the usual association of diabetes with obesity. To understand the...

Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle

Kim, Jason K., Michael, M. Dodson, Previs, Stephen F., Peroni, Odile D., Mauvais-Jarvis, Franck, Neschen, Susanne, ...

Obesity and insulin resistance in skeletal muscle are two major factors in the pathogenesis of type 2 diabetes. Mice with muscle-specific inactivation of the insulin receptor gene (MIRKO) are...

Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation

Gao, Qian, Wolfgang, Michael J., Neschen, Susanne, Morino, Katsutaro, Horvath, Tamas L., Shulman, Gerald I., ...

Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. STAT3 has been implicated in the control of neuron/glial differentiation and...

Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity

Dresner, Alan, Laurent, Didier, Marcucci, Melissa, Griffin, Margaret E., Dufour, Sylvie, Cline, Gary W., ...

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...

PKC-θ knockout mice are protected from fat-induced insulin resistance

Kim, Jason K., Fillmore, Jonathan J., Sunshine, Mary Jean, Albrecht, Bjoern, Higashimori, Takamasa, Kim, Dong-Wook, ...

Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations in fat metabolism. Recent studies have suggested that local accumulation of fat...

Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents

Morino, Katsutaro, Petersen, Kitt Falk, Dufour, Sylvie, Befroy, Douglas, Frattini, Jared, Shatzkes, Nadine, ...

To further explore the nature of the mitochondrial dysfunction and insulin resistance that occur in the muscle of young, lean, normoglycemic, insulin-resistant offspring of parents with type 2...

Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2

Savage, David B., Choi, Cheol Soo, Samuel, Varman T., Liu, Zhen-Xiang, Zhang, Dongyan, Wang, Amy, ...

Hepatic steatosis is a core feature of the metabolic syndrome and type 2 diabetes and leads to hepatic insulin resistance. Malonyl-CoA, generated by acetyl-CoA carboxylases 1 and 2 (Acc1 and Acc2),...

Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes

Fernández, Ana M., Kim, Jason K., Yakar, Shoshana, Dupont, Joëlle, Hernandez-Sanchez, Catalina, Castle, Arthur L., ...

Peripheral insulin resistance and impaired insulin action are the primary characteristics of type 2 diabetes. The first observable defect in this major disorder occurs in muscle, where glucose...

Assessment of mitochondrial energy coupling in vivo by 13C/31P NMR

Jucker, Beat M., Dufour, Sylvie, Ren, Jianming, Cao, Xueying, Previs, Stephen F., Underhill, Brian, ...

The recently cloned uncoupling protein homolog UCP3 is expressed primarily in muscle and therefore may play a significant role in the regulation of energy expenditure and body weight. However,...

Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR

Shen, Jun, Petersen, Kitt F., Behar, Kevin L., Brown, Peter, Nixon, Terrence W., Mason, Graeme F., ...

Recent 13C NMR studies in rat models have shown that the glutamate/glutamine cycle is highly active in the cerebral cortex and is coupled to incremental glucose oxidation in an ≈1:1 stoichiometry....

Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance

Zabolotny, Janice M., Kim, Young-Bum, Peroni, Odile D., Kim, Jason K., Pani, Michael A., Boss, Olivier, ...

Previous reports indicate that the expression and/or activity of the protein-tyrosine phosphatase (PTP) LAR are increased in insulin-responsive tissues of obese, insulin-resistant humans and rodents,...

Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance

Kim, Jason K., Fillmore, Jonathan J., Chen, Yan, Yu, Chunli, Moore, Irene K., Pypaert, Marc, ...

Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to...

Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice

Klaman, Lori D., Boss, Olivier, Peroni, Odile D., Kim, Jason K., Martino, Jennifer L., Zabolotny, Janice M., ...

Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To...

AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation

Zong, Haihong, Ren, Jian Ming, Young, Lawrence H., Pypaert, Marc, Mu, James, Birnbaum, Morris J., ...

Mitochondrial biogenesis is a critical adaptation to chronic energy deprivation, yet the signaling mechanisms responsible for this response are poorly understood. To examine the role of AMP-activated...

Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes

Hundal, Ripudaman S., Petersen, Kitt F., Mayerson, Adam B., Randhawa, Pritpal S., Inzucchi, Silvio, Shoelson, Steven E., ...

Recent studies have implicated fatty acid-dependent activation of the serine kinase IKKβ, which plays a key role in tissue inflammation, in the pathogenesis of insulin resistance. High doses of...

Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy

Petersen, Kitt Falk, Oral, Elif Arioglu, Dufour, Sylvie, Befroy, Douglas, Ariyan, Charlotte, Yu, Chunli, ...

Lipodystrophy is a rare disorder that is characterized by selective loss of subcutaneous and visceral fat and is associated with hypertriglyceridemia, hepatomegaly, and disordered glucose metabolism....

Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways

Rui, Liangyou, Aguirre, Vincent, Kim, Jason K., Shulman, Gerald I., Lee, Anna, Corbould, Anne, ...

Serine/threonine phosphorylation of IRS-1 might inhibit insulin signaling, but the relevant phosphorylation sites are difficult to identify in cultured cells and to validate in isolated tissues....

Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance

Yang, Chunmei, Coker, Kenneth J., Kim, Jason K., Mora, Silvia, Thurmond, Debbie C., Davis, Ann C., ...

To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4–knockout mice. Homozygotic disruption...

Prevention of fat-induced insulin resistance by salicylate

Kim, Jason K., Kim, Yoon-Jung, Fillmore, Jonathan J., Chen, Yan, Moore, Irene, Lee, Jongsoon, ...

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation of a serine kinase cascade involving IKK-β. To test this hypothesis, we first...

Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle

Lebon, Vincent, Dufour, Sylvie, Petersen, Kitt Falk, Ren, Jianming, Jucker, Beat M., Slezak, Lori A., ...

The mechanism underlying the regulation of basal metabolic rate by thyroid hormone remains unclear. Although it has been suggested that thyroid hormone might uncouple substrate oxidation from ATP...

Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes

Fernández, Ana M., Kim, Jason K., Yakar, Shoshana, Dupont, Joëlle, Hernandez-Sanchez, Catalina, Castle, Arthur L., ...

Peripheral insulin resistance and impaired insulin action are the primary characteristics of type 2 diabetes. The first observable defect in this major disorder occurs in muscle, where glucose...

Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle

Kim, Jason K., Gimeno, Ruth E., Higashimori, Takamasa, Kim, Hyo-Jeong, Choi, Hyejeong, Punreddy, Sandhya, ...

Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid...

Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4

Kim, Jason K., Zisman, Ariel, Fillmore, Jonathan J., Peroni, Odile D., Kotani, Ko, Perret, Pascale, ...

Using cre/loxP gene targeting, transgenic mice with muscle-specific inactivation of the GLUT4 gene (muscle GLUT4 KO) were generated and shown to develop a diabetes phenotype. To determine the...

Glucose Disposal during Insulinopenia in Somatostatin-Treated Dogs: THE ROLES OF GLUCOSE AND GLUCAGON

Shulman, Gerald I., Liljenquist, John E., Williams, Phillip E., Lacy, William W., Cherrington, Alan D.

The first aim of this study was to determine whether the plasma glucose level can regulate hepatic glucose balance in vivo independent of its effects on insulin and glucagon secretion. To accomplish...

Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice

Gavrilova, Oksana, Marcus-Samuels, Bernice, Graham, David, Kim, Jason K., Shulman, Gerald I., Castle, Arthur L., ...

In lipoatrophic diabetes, a lack of fat is associated with insulin resistance and hyperglycemia. This is in striking contrast to the usual association of diabetes with obesity. To understand the...

Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle

Kim, Jason K., Michael, M. Dodson, Previs, Stephen F., Peroni, Odile D., Mauvais-Jarvis, Franck, Neschen, Susanne, ...

Obesity and insulin resistance in skeletal muscle are two major factors in the pathogenesis of type 2 diabetes. Mice with muscle-specific inactivation of the insulin receptor gene (MIRKO) are...

Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation

Gao, Qian, Wolfgang, Michael J., Neschen, Susanne, Morino, Katsutaro, Horvath, Tamas L., Shulman, Gerald I., ...

Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. STAT3 has been implicated in the control of neuron/glial differentiation and...

Effects of free fatty acids on glucose transport and IRS-1–associated phosphatidylinositol 3-kinase activity

Dresner, Alan, Laurent, Didier, Marcucci, Melissa, Griffin, Margaret E., Dufour, Sylvie, Cline, Gary W., ...

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...

PKC-θ knockout mice are protected from fat-induced insulin resistance

Kim, Jason K., Fillmore, Jonathan J., Sunshine, Mary Jean, Albrecht, Bjoern, Higashimori, Takamasa, Kim, Dong-Wook, ...

Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations in fat metabolism. Recent studies have suggested that local accumulation of fat...

Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents

Morino, Katsutaro, Petersen, Kitt Falk, Dufour, Sylvie, Befroy, Douglas, Frattini, Jared, Shatzkes, Nadine, ...

To further explore the nature of the mitochondrial dysfunction and insulin resistance that occur in the muscle of young, lean, normoglycemic, insulin-resistant offspring of parents with type 2...

Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2

Savage, David B., Choi, Cheol Soo, Samuel, Varman T., Liu, Zhen-Xiang, Zhang, Dongyan, Wang, Amy, ...

Hepatic steatosis is a core feature of the metabolic syndrome and type 2 diabetes and leads to hepatic insulin resistance. Malonyl-CoA, generated by acetyl-CoA carboxylases 1 and 2 (Acc1 and Acc2),...

Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease

Samuel, Varman T., Liu, Zhen-Xiang, Wang, Amy, Beddow, Sara A., Geisler, John G., Kahn, Mario, ...

Nonalcoholic fatty liver disease is strongly associated with hepatic insulin resistance and type 2 diabetes mellitus, but the molecular signals linking hepatic fat accumulation to hepatic insulin...

Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle

Chen, Alon, Brar, Bhawanjit, Choi, Cheol Soo, Rousso, David, Vaughan, Joan, Kuperman, Yael, ...

Skeletal muscle is the principal tissue responsible for insulin-stimulated glucose disposal and is a major site of peripheral insulin resistance. Urocortin 2 (Ucn 2), a member of the...

Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men

Petersen, Kitt Falk, Dufour, Sylvie, Feng, Jing, Befroy, Douglas, Dziura, James, Man, Chiara Dalla, ...

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity in most, but not all, ethnic groups, suggesting important ethnic differences in disease susceptibility. Although it is clear that...

Aging-Associated Reductions in AMP-Activated Protein Kinase Activity and Mitochondrial Biogenesis

Reznick, Richard M., Zong, Haihong, Li, Ji, Morino, Katsutaro, Moore, Irene K., Yu, Hannah J., ...

Recent studies have demonstrated a strong relationship between aging-associated reductions in mitochondrial function, dysregulated intracellular lipid metabolism, and insulin resistance. Given the...

Interethnic Differences in Muscle, Liver and Abdominal Fat Partitioning in Obese Adolescents

Liska, David, Dufour, Sylvie, Zern, Tosca L., Taksali, Sara, Calí, Anna M.G., Dziura, James, ...

The prevalence of insulin resistance and type 2 diabetes (T2D) in obese youth is rapidly increasing, especially in Hispanics and African Americans compared to Caucasians. Insulin resistance is known...

The role of AMP-activated protein kinase in mitochondrial biogenesis

Reznick, Richard M, Shulman, Gerald I

While it has been known for more than 75 years that physical activity is associated with increased mitochondrial content in muscle, the molecular mechanism for this adaptive process has only recently...

Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance

Choi, Cheol Soo, Fillmore, Jonathan J., Kim, Jason K., Liu, Zhen-Xiang, Kim, Sheene, Collier, Emily F., ...

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and is strongly associated with obesity. Increased concentrations of intracellular fatty acid metabolites have been...

Muscle-specific knockout of PKC-λ impairs glucose transport and induces metabolic and diabetic syndromes

Farese, Robert V., Sajan, Mini P., Yang, Hong, Li, Pengfei, Mastorides, Steven, Gower, William R., ...

Obesity, the metabolic syndrome, and type 2 diabetes mellitus (T2DM) are major global health problems. Insulin resistance is frequently present in these disorders, but the causes and effects of such...

Obesity-associated improvements in metabolic profile through expansion of adipose tissue

Kim, Ja-Young, Van De Wall, Esther, Laplante, Mathieu, Azzara, Anthony, Trujillo, Maria E., Hofmann, Susanna M., ...

Excess caloric intake can lead to insulin resistance. The underlying reasons are complex but likely related to ectopic lipid deposition in nonadipose tissue. We hypothesized that the inability to...

Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo

Hurov, Jonathan B., Huang, Mei, White, Lynn S., Lennerz, Jochen, Choi, Cheol Soo, Cho, You-Ree, ...

Obesity is a major factor central to the development of insulin resistance and type 2 diabetes. The identification and characterization of genes involved in regulation of adiposity, insulin...

Abnormal glucose homeostasis in skeletal muscle–specific PGC-1α knockout mice reveals skeletal muscle–pancreatic β cell crosstalk

Handschin, Christoph, Choi, Cheol Soo, Chin, Sherry, Kim, Sheene, Kawamori, Dan, Kurpad, Amarnath J., ...

The transcriptional coactivator PPARγ coactivator 1α (PGC-1α) is a strong activator of mitochondrial biogenesis and oxidative metabolism. While expression of PGC-1α and many of its mitochondrial...

The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome

Petersen, Kitt Falk, Dufour, Sylvie, Savage, David B., Bilz, Stefan, Solomon, Gina, Yonemitsu, Shin, ...

We examined the hypothesis that insulin resistance in skeletal muscle promotes the development of atherogenic dyslipidemia, associated with the metabolic syndrome, by altering the distribution...

A Prevalent Variant in PPP1R3A Impairs Glycogen Synthesis and Reduces Muscle Glycogen Content in Humans and Mice

Savage, David B, Zhai, Lanmin, Ravikumar, Balasubramanian, Choi, Cheol Soo, Snaar, Johanna E, McGuire, Amanda C, ...

Stephen O'Rahilly and colleagues describe the effect of a mutation inPPP1R3A, present in 1.36% of participants from one UK population, that directly impairs glycogen synthesis and decreases glycogen...

Continuous fat oxidation in acetyl–CoA carboxylase 2 knockout mice increases total energy expenditure, reduces fat mass, and improves insulin sensitivity

Choi, Cheol Soo, Savage, David B., Abu-Elheiga, Lutfi, Liu, Zhen-Xiang, Kim, Sheene, Kulkarni, Ameya, ...

Acetyl–CoA carboxylase 2 (ACC)2 is a key regulator of mitochondrial fat oxidation. To examine the impact of ACC2 deletion on whole-body energy metabolism, we measured changes in substrate oxidation...

Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance

Zhang, Dongyan, Liu, Zhen-Xiang, Choi, Cheol Soo, Tian, Liqun, Kibbey, Richard, Dong, Jianying, ...

Alterations in mitochondrial function have been implicated in the pathogenesis of insulin resistance and type 2 diabetes. However, it is unclear whether the reduced mitochondrial function is a...

Regulation of hypothalamic malonyl-CoA by central glucose and leptin

Wolfgang, Michael J., Cha, Seung Hun, Sidhaye, Aniket, Chohnan, Shigeru, Cline, Gary, Shulman, Gerald I., ...

Hypothalamic malonyl-CoA has been shown to function in global energy homeostasis by modulating food intake and energy expenditure. Little is known, however, about the regulation of malonyl-CoA...

Increased substrate oxidation and mitochondrial uncoupling in skeletal muscle of endurance-trained individuals

Befroy, Douglas E., Petersen, Kitt Falk, Dufour, Sylvie, Mason, Graeme F., Rothman, Douglas L., Shulman, Gerald I.

Endurance exercise training is accompanied by physiological changes that improve muscle function and performance. Several studies have demonstrated that markers of mitochondrial capacity are...

Paradoxical effects of increased expression of PGC-1α on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism

Choi, Cheol Soo, Befroy, Douglas E., Codella, Roberto, Kim, Sheene, Reznick, Richard M., Hwang, Yu-Jin, ...

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α has been shown to play critical roles in regulating mitochondria biogenesis, respiration, and muscle oxidative phenotype....

Reduced heart size and increased myocardial fuel substrate oxidation in ACC2 mutant mice

Essop, M. Faadiel, Camp, Heidi S., Choi, Cheol Soo, Sharma, Saumya, Fryer, Ryan M., Reinhart, Glenn A., ...

The cardiac-enriched isoform of acetyl-CoA carboxylase (ACC2) is a key regulator of mitochondrial fatty acid (FA) uptake via carnitine palmitoyltransferase 1 (CPT1). To test the hypothesis that...

SirT1 knockdown in liver decreases basal hepatic glucose production and increases hepatic insulin responsiveness in diabetic rats

Erion, Derek M., Yonemitsu, Shin, Nie, Yongzhan, Nagai, Yoshio, Gillum, Matthew P., Hsiao, Jennifer J., ...

Hepatic gluconeogenesis is a major contributing factor to hyperglycemia in the fasting and postprandial states in type 2 diabetes mellitus (T2DM). Because Sirtuin 1 (SirT1) induces hepatic...

Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes

Samuel, Varman T., Beddow, Sara A., Iwasaki, Takanori, Zhang, Xian-Man, Chu, Xin, Still, Christopher D., ...

Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is attributed to increased hepatic gluconeogenesis, which has been ascribed to increased transcriptional expression of...

Muscle-Specific IRS-1 Ser→Ala Transgenic Mice Are Protected From Fat-Induced Insulin Resistance in Skeletal Muscle

Morino, Katsutaro, Neschen, Susanne, Bilz, Stefan, Sono, Saki, Tsirigotis, Dimitrios, Reznick, Richard M., ...

OBJECTIVE—Insulin resistance in skeletal muscle plays a critical role in the pathogenesis of type 2 diabetes, yet the cellular mechanisms responsible for insulin resistance are poorly understood....