Published in Proc Natl Acad Sci U S A on February 29, 2000
Intracellular signalling pathways activated by leptin. Biochem J (2006) 2.93
Making insulin-deficient type 1 diabetic rodents thrive without insulin. Proc Natl Acad Sci U S A (2008) 2.12
Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab (2011) 1.99
Disruption of leptin receptor expression in the pancreas directly affects beta cell growth and function in mice. J Clin Invest (2007) 1.99
Tissue-specific dysregulation of DNA methylation in aging. Aging Cell (2010) 1.90
Role of leptin as an immunomodulator of blood mononuclear cells: mechanisms of action. Clin Exp Immunol (2003) 1.65
Brain insulin: regulation, mechanisms of action and functions. Cell Mol Neurobiol (2003) 1.42
Leptin's role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals. Endocr Rev (2013) 1.10
Leptin therapy reverses hyperglycemia in mice with streptozotocin-induced diabetes, independent of hepatic leptin signaling. Diabetes (2011) 1.10
Adiponectin activation of AMPK disrupts leptin-mediated hepatic fibrosis via suppressors of cytokine signaling (SOCS-3). J Cell Biochem (2010) 1.07
Leptin promotes cell survival and activates Jurkat T lymphocytes by stimulation of mitogen-activated protein kinase. Clin Exp Immunol (2008) 0.99
Leptin repletion restores depressed {beta}-adrenergic contractility in ob/ob mice independently of cardiac hypertrophy. J Physiol (2005) 0.98
Cross down-regulation of leptin and insulin receptor expression and signalling in a human neuronal cell line. Biochem J (2005) 0.96
Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays; a benefit beyond weight and appetite regulation. Peptides (2009) 0.96
Dietary fish oil exerts hypolipidemic effects in lean and insulin sensitizing effects in obese LDLR-/- mice. J Nutr (2009) 0.93
Disruption of hepatic leptin signaling protects mice from age- and diet-related glucose intolerance. Diabetes (2010) 0.92
Differential Role of Leptin and Adiponectin in Cardiovascular System. Int J Endocrinol (2015) 0.92
The role of leptin in glucose homeostasis. J Diabetes Investig (2012) 0.90
Leptin signaling: A key pathway in immune responses. Curr Signal Transduct Ther (2009) 0.88
Pharmacological effects of lipid-lowering drugs on circulating adipokines. World J Diabetes (2010) 0.84
The role of psychobiological and neuroendocrine mechanisms in appetite regulation and obesity. Open Cardiovasc Med J (2012) 0.81
Metreleptin improves blood glucose in patients with insulin receptor mutations. J Clin Endocrinol Metab (2013) 0.79
Leptin stimulates sympathetic axon outgrowth. Neurosci Lett (2014) 0.78
Sam68 Mediates the Activation of Insulin and Leptin Signalling in Breast Cancer Cells. PLoS One (2016) 0.75
Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway. Nutr Diabetes (2016) 0.75
Metabolic and adaptive immune responses induced in mice infected with tissue-dwelling nematode Trichinella zimbabwensis. Open Vet J (2016) 0.75
The glucoregulatory actions of leptin. Mol Metab (2017) 0.75
Positional cloning of the mouse obese gene and its human homologue. Nature (1994) 38.85
Leptin and the regulation of body weight in mammals. Nature (1998) 14.84
Disruption of IRS-2 causes type 2 diabetes in mice. Nature (1998) 7.94
Abnormal splicing of the leptin receptor in diabetic mice. Nature (1996) 7.71
Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature (1997) 7.33
Jaks and STATs: biological implications. Annu Rev Immunol (1998) 7.18
Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature (1994) 6.50
Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes (1994) 4.30
Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. EMBO J (1993) 3.51
Role of IRS-2 in insulin and cytokine signalling. Nature (1995) 3.23
Acute stimulation of glucose metabolism in mice by leptin treatment. Nature (1997) 3.12
Divergent signaling capacities of the long and short isoforms of the leptin receptor. J Biol Chem (1997) 3.01
Construction and characterization of a conditionally active version of the serine/threonine kinase Akt. J Biol Chem (1998) 2.93
Modulation of insulin activities by leptin. Science (1996) 2.92
Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett (1992) 2.52
Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway. J Biol Chem (1999) 2.28
Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse. J Clin Invest (1997) 2.11
The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med (1999) 2.05
Differential signaling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1-deficient cells. Mol Cell Biol (1997) 2.02
Glycogen synthase kinase 3 is an insulin-regulated C/EBPalpha kinase. Mol Cell Biol (1999) 1.92
Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. J Biol Chem (1995) 1.82
Intracerebroventricular leptin regulates hepatic but not peripheral glucose fluxes. J Biol Chem (1998) 1.80
Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action. J Biol Chem (1997) 1.61
Identification of multifunctional ATP-citrate lyase kinase as the alpha-isoform of glycogen synthase kinase-3. Biochem J (1992) 1.60
Dynamics of insulin signaling in 3T3-L1 adipocytes. Differential compartmentalization and trafficking of insulin receptor substrate (IRS)-1 and IRS-2. J Biol Chem (1998) 1.54
Structural organization and alternative splicing of the murine phosphoinositide 3-kinase p85 alpha gene. Genomics (1996) 1.47
Plasma leptin and insulin relationships in obese and nonobese humans. Diabetes (1996) 1.47
Transcriptional activity of heat shock factor 1 at 37 degrees C is repressed through phosphorylation on two distinct serine residues by glycogen synthase kinase 3 and protein kinases Calpha and Czeta. J Biol Chem (1998) 1.45
Leptin action in intestinal cells. J Biol Chem (1998) 1.41
Leptin receptor (OB-R) signaling. Cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization. J Biol Chem (1997) 1.38
The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line. Mol Endocrinol (1997) 1.35
The COOH-terminal tyrosine phosphorylation sites on IRS-1 bind SHP-2 and negatively regulate insulin signaling. J Biol Chem (1998) 1.35
Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor. Proc Natl Acad Sci U S A (1998) 1.30
Leptin receptor action in hepatic cells. J Biol Chem (1997) 1.29
Downstream signalling events regulated by phosphatidylinositol 3-kinase activity. Cell Signal (1998) 1.28
Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction. Proc Natl Acad Sci U S A (1999) 1.23
Regulation of body weight in humans. Physiol Rev (1999) 1.22
Insulin and exercise decrease glycogen synthase kinase-3 activity by different mechanisms in rat skeletal muscle. J Biol Chem (1999) 1.13
Leptin stimulates glucose transport and glycogen synthesis in C2C12 myotubes: evidence for a P13-kinase mediated effect. Diabetologia (1997) 1.12
Leptin activation in hypothalamus. Nature (1996) 1.09
Leptin expression and action: new experimental paradigms. Proc Natl Acad Sci U S A (1997) 1.07
Enhanced insulin-stimulated activation of phosphatidylinositol 3-kinase in the liver of high-fat-fed rats. Diabetes (1999) 0.99
Transmembrane domain of the AEV erb B oncogene protein is not required for partial manifestation of the transformed phenotype. Virology (1987) 0.97
Acute intravenous leptin infusion increases glucose turnover but not skeletal muscle glucose uptake in ob/ob mice. Diabetes (1999) 0.92
Acute effect of leptin on hepatic glycogenolysis and gluconeogenesis in perfused rat liver. Hepatology (1999) 0.92
Leptin enhances glycogen storage in hepatocytes by inhibition of phosphorylase and exerts an additive effect with insulin. Diabetes (1999) 0.92
Insulin's regulation of c-fos gene transcription in hepatoma cells. J Biol Chem (1990) 0.89
13C NMR study of the effects of leptin treatment on kinetics of hepatic intermediary metabolism. Proc Natl Acad Sci U S A (1998) 0.85
Thyroid hormone nuclear receptor levels are influenced by the acetylation of chromatin-associated proteins. J Biol Chem (1980) 0.84
Leptin does not affect adipocyte glucose metabolism: studies in fresh and cultured adipocytes. Metabolism (1998) 0.77
Insulin signalling and the regulation of glucose and lipid metabolism. Nature (2001) 16.41
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature (2001) 11.72
Role of brain insulin receptor in control of body weight and reproduction. Science (2000) 8.14
A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell (1998) 8.10
Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell (2000) 7.26
Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell (1999) 6.53
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature (1991) 6.50
Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature (1994) 6.50
Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet (1992) 6.28
The insulin signaling system. J Biol Chem (1994) 5.25
Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol Cell Biol (1994) 5.13
The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med (1976) 5.09
Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor. Science (1982) 5.01
Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med (1990) 4.87
Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus. Am J Cardiol (1987) 4.27
Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles. Cell (1997) 4.20
Insulin stimulates tyrosine phosphorylation of the insulin receptor in a cell-free system. Nature (1982) 3.90
Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest (2000) 3.79
Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells. Nature (1985) 3.57
Membrane receptors for hormones and neurotransmitters. J Cell Biol (1976) 3.54
Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med (2000) 3.53
The changing natural history of nephropathy in type I diabetes. Am J Med (1985) 3.50
Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat Genet (2001) 3.50
Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance. J Clin Invest (1999) 3.36
Direct demonstration that receptor crosslinking or aggregation is important in insulin action. Proc Natl Acad Sci U S A (1978) 3.15
beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. Nat Genet (2002) 3.12
Quantitative aspects of the insulin-receptor interaction in liver plasma membranes. J Biol Chem (1974) 3.04
Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J Clin Invest (2000) 3.01
Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance. Science (1975) 2.97
Bidirectional modulation of insulin action by amino acids. J Clin Invest (1998) 2.92
A cascade of tyrosine autophosphorylation in the beta-subunit activates the phosphotransferase of the insulin receptor. J Biol Chem (1988) 2.90
Insulin action and the insulin signaling network. Endocr Rev (1995) 2.89
Insulin-receptor interaction in the obese-hyperglycemic mouse. A model of insulin resistance. J Biol Chem (1973) 2.80
Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. J Clin Invest (2000) 2.75
Insulin stimulation of phosphorylation of the beta subunit of the insulin receptor. Formation of both phosphoserine and phosphotyrosine. J Biol Chem (1982) 2.58
Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression. Nat Genet (1999) 2.57
Rad: a member of the Ras family overexpressed in muscle of type II diabetic humans. Science (1993) 2.57
Tyrosine-specific protein kinase activity is associated with the purified insulin receptor. Proc Natl Acad Sci U S A (1983) 2.49
Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines. J Clin Invest (1999) 2.48
125I-insulin binding to cultured human lymphocytes. Initial localization and fate of hormone determined by quantitative electron microscopic autoradiography. J Clin Invest (1978) 2.47
Evidence for a circulating islet cell growth factor in insulin-resistant states. Proc Natl Acad Sci U S A (2001) 2.44
Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha. Nat Genet (2000) 2.39
Insulin resistance, insulin insensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism (1978) 2.36
Regulation of insulin receptor substrate-1 in liver and muscle of animal models of insulin resistance. J Clin Invest (1992) 2.31
Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. N Engl J Med (1984) 2.26
Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A (1995) 2.25
Insulin-induced receptor loss in cultured human lymphocytes is due to accelerated receptor degradation. Proc Natl Acad Sci U S A (1981) 2.18
Direct demonstration of separate receptors for growth and metabolic activities of insulin and multiplication-stimulating activity (an insulinlike growth factor) using antibodies to the insulin receptor. J Clin Invest (1980) 2.15
Essential role of insulin receptor substrate 1 in differentiation of brown adipocytes. Mol Cell Biol (2001) 2.14
beta(3)-adrenergic stimulation differentially inhibits insulin signaling and decreases insulin-induced glucose uptake in brown adipocytes. J Biol Chem (1999) 2.13
Fluctuations in the affinity and concentration of insulin receptors on circulating monocytes of obese patients: effects of starvation, refeeding, and dieting. J Clin Invest (1976) 2.12
The molecular mechanism of insulin action. Annu Rev Med (1985) 2.12
Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse. J Clin Invest (1997) 2.11
Phorbol esters modulate insulin receptor phosphorylation and insulin action in cultured hepatoma cells. Proc Natl Acad Sci U S A (1984) 2.09
Insulin stimulation of phosphatidylinositol 3-kinase activity and association with insulin receptor substrate 1 in liver and muscle of the intact rat. J Biol Chem (1992) 2.06
Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity. Cell (1988) 2.06
Differential signaling by insulin receptor substrate 1 (IRS-1) and IRS-2 in IRS-1-deficient cells. Mol Cell Biol (1997) 2.02
Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4. J Clin Invest (2001) 2.01
Receptors and growth-promoting effects of insulin and insulinlike growth factors on cells from bovine retinal capillaries and aorta. J Clin Invest (1985) 2.00
Expression and function of IRS-1 in insulin signal transmission. J Biol Chem (1992) 1.98
Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med (1998) 1.93
The riddle of tumour hypoglycaemia revisited. Clin Endocrinol Metab (1980) 1.91
Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk. J Clin Invest (1997) 1.88
Effects of autoantibodies to the insulin receptor on isolated adipocytes. Studies of insulin binding and insulin action. J Clin Invest (1977) 1.85
Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy. J Med Genet (2002) 1.84
Demonstration that monocytes rather than lymphocytes are the insulin-binding cells in preparations of humah peripheral blood mononuclear leukocytes: implications for studies of insulin-resistant states in man. Proc Natl Acad Sci U S A (1975) 1.83
Cross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci U S A (1996) 1.81
Insulin receptor deficiency in genetic and acquired obesity. J Clin Invest (1975) 1.79
Characterization of antibodies to the insulin receptor: a cause of insulin-resistant diabetes in man. J Clin Invest (1976) 1.74
Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity. J Biol Chem (1988) 1.74
Insulin receptors, receptor antibodies, and the mechanism of insulin action. Recent Prog Horm Res (1981) 1.68
Essential role of insulin receptor substrate-2 in insulin stimulation of Glut4 translocation and glucose uptake in brown adipocytes. J Biol Chem (2000) 1.67
Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells. Mol Cell (2001) 1.65
Positive and negative regulation of phosphoinositide 3-kinase-dependent signaling pathways by three different gene products of the p85alpha regulatory subunit. Mol Cell Biol (2000) 1.65
Direct demonstration of glycosylation of insulin receptor subunits by biosynthetic and external labeling: evidence for heterogeneity. Proc Natl Acad Sci U S A (1981) 1.64
Characterization of insulin-mediated phosphorylation of the insulin receptor in a cell-free system. J Biol Chem (1983) 1.62
Biosynthesis and glycosylation of the insulin receptor. Evidence for a single polypeptide precursor of the two major subunits. J Biol Chem (1983) 1.62
Purification and partial sequence analysis of pp185, the major cellular substrate of the insulin receptor tyrosine kinase. J Biol Chem (1991) 1.62
Modulation of insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of dexamethasone-treated rats. J Clin Invest (1993) 1.61
Epidemiologic approach to the etiology of type I diabetes mellitus and its complications. N Engl J Med (1987) 1.58
Characterization of the insulin receptor in its membrane environment by radiation inactivation. J Biol Chem (1980) 1.58
4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice. J Biol Chem (1995) 1.56
Kinetic properties and sites of autophosphorylation of the partially purified insulin receptor from hepatoma cells. J Biol Chem (1984) 1.56
A model to explore the interaction between muscle insulin resistance and beta-cell dysfunction in the development of type 2 diabetes. Diabetes (2000) 1.55
Thymic lymphocytes in obese (ob-ob) mice. A mirror of the insulin receptor defect in liver and fat. J Biol Chem (1974) 1.55
Dynamics of insulin signaling in 3T3-L1 adipocytes. Differential compartmentalization and trafficking of insulin receptor substrate (IRS)-1 and IRS-2. J Biol Chem (1998) 1.54
Increased expression of mitochondrial-encoded genes in skeletal muscle of humans with diabetes mellitus. J Clin Invest (1995) 1.53
Insulin-stimulated translocation of GLUT4 glucose transporters requires SNARE-complex proteins. Proc Natl Acad Sci U S A (1996) 1.52
The role of insulin and IGF-1 signaling in longevity. Cell Mol Life Sci (2005) 1.52
Insulin-induced dissociation of its receptor into subunits: possible molecular concomitant of negative cooperativity. Biochem Biophys Res Commun (1976) 1.51
A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies. J Clin Invest (1996) 1.50
The fate of insulin bound to adipocytes. Evidence for compartmentalization and processing. J Biol Chem (1978) 1.50
Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice. J Clin Invest (1999) 1.50
Insulin stimulation of phosphatidylinositol 3-kinase activity maps to insulin receptor regions required for endogenous substrate phosphorylation. J Biol Chem (1992) 1.50
Overexpression of Rad inhibits glucose uptake in cultured muscle and fat cells. J Biol Chem (1996) 1.49
Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain. Mol Cell Biol (1996) 1.49
Regulation of insulin receptors and insulin responsiveness in 3T3-L1 fatty fibroblasts. Endocrinology (1979) 1.49
Risk of proliferative diabetic retinopathy in juvenile-onset type I diabetes: a 40-yr follow-up study. Diabetes Care (1986) 1.48
Receptors for insulin, NSILA-s, and growth hormone: applications to disease states in man. Recent Prog Horm Res (1975) 1.47
Predominance of tyrosine phosphorylation of insulin receptors during the initial response of intact cells to insulin. J Biol Chem (1985) 1.45