Insulin resistance--mechanisms, syndromes, and implications.

The past 20 years have witnessed a remarkable increase in our knowledge of the cellular and molecular mechanisms that underlie the diverse actions of insulin, the central hormone of metabolic regulation. Interest in the molecular details of insulin action has been heightened by the prevalence of insulin resistance and by the fact that insulin resistance has a key role in the pathogenesis of many disorders, including obesity, diabetes mellitus, ovarian hyperan-drogenism, and possibly hypertension. In this review, we discuss current concepts of the mechanisms of insulin action and insulin resistance and the implications of insulin resistance for a variety of . . .

[1]  C. Kahn,et al.  Receptors for insulin, NSILA-s, and growth hormone: applications to disease states in man. , 1975, Recent progress in hormone research.

[2]  S. Hager Insulin resistance of uremia. , 1989, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[3]  A. Ullrich,et al.  Functionally distinct insulin receptors generated by tissue‐specific alternative splicing. , 1990, The EMBO journal.

[4]  M. Cassader,et al.  Mechanism of insulin resistance in human liver cirrhosis. Evidence of a combined receptor and postreceptor defect. , 1985, The Journal of clinical investigation.

[5]  S. Lillioja,et al.  Glucose storage is a major determinant of in vivo "insulin resistance" in subjects with normal glucose tolerance. , 1986, The Journal of clinical endocrinology and metabolism.

[6]  E. Lander,et al.  A mutation in the insulin receptor gene that impairs transport of the receptor to the plasma membrane and causes insulin‐resistant diabetes. , 1989, The EMBO journal.

[7]  Joseph Schlessinger,et al.  Signal transduction by receptors with tyrosine kinase activity , 1990, Cell.

[8]  Simeon I. Taylor,et al.  A nonsense mutation causing decreased levels of insulin receptor mRNA: detection by a simplified technique for direct sequencing of genomic DNA amplified by the polymerase chain reaction. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[9]  C. Kahn,et al.  Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance , 1975, Science.

[10]  A. Kosaki,et al.  Insulin-resistant diabetes due to a point mutation that prevents insulin proreceptor processing. , 1988, Science.

[11]  C. Kahn,et al.  Heterogeneity of the insulin-receptor interaction in lipoatropic diabetes. , 1981, The Journal of clinical endocrinology and metabolism.

[12]  D. Neville,et al.  Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[13]  C. Kahn,et al.  The evolving clinical course of patients with insulin receptor autoantibodies: spontaneous remission or receptor proliferation with hypoglycemia. , 1978, The Journal of clinical endocrinology and metabolism.

[14]  R. DeFronzo The Triumvirate: β-Cell, Muscle, Liver: A Collusion Responsible for NIDDM , 1988, Diabetes.

[15]  G. Bell,et al.  Identification of a ligand-binding region of the human insulin receptor encoded by the second exon of the gene. , 1990, Molecular endocrinology.

[16]  R. Barbieri,et al.  The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. , 1988, Fertility and sterility.

[17]  G I Bell,et al.  Molecular Biology of Mammalian Glucose Transporters , 1990, Diabetes Care.

[18]  C. Kahn,et al.  Insulin receptor function in fibroblasts from patients with leprechaunism. Differential alterations in binding, autophosphorylation, kinase activity, and receptor-mediated internalization. , 1988, The Journal of clinical investigation.

[19]  C. Kahn,et al.  Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein , 1991, Nature.

[20]  J. Olefsky,et al.  Glucose and insulin co-regulate the glucose transport system in primary cultured adipocytes. A new mechanism of insulin resistance. , 1987, The Journal of biological chemistry.

[21]  S. Rabson,et al.  Familial hypertrophy of pineal body, hyperplasia of adrenal cortex and diabetes mellitus; report of 3 cases. , 1956, American journal of clinical pathology.

[22]  S. Lillioja,et al.  The amino acid sequence of the insulin receptor is normal in an insulin-resistant Pima Indian. , 1990, The Journal of clinical endocrinology and metabolism.

[23]  P. Usher,et al.  Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Steiner,et al.  Lessons Learned From Molecular Biology of Insulin-Gene Mutations , 1990, Diabetes Care.

[25]  R. DeFronzo,et al.  Effect of fatty acids on glucose production and utilization in man. , 1983, The Journal of clinical investigation.

[26]  J. Flier,et al.  Tissue-specific expression of two alternatively spliced insulin receptor mRNAs in man. , 1989, Molecular endocrinology.

[27]  P. H. Seeburg,et al.  Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes , 1985, Nature.

[28]  P. Gorden,et al.  Lupus nephritis and other autoimmune features in patients with diabetes mellitus due to autoantibody to insulin receptors. , 1985, Annals of internal medicine.

[29]  G. Pagès,et al.  Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity , 1989, Cell.

[30]  J. Flier,et al.  Regulation of Glucose-Transporter Gene Expression In Vitro and In Vivo , 1990, Diabetes Care.

[31]  D. Accili,et al.  Syndromes of autoimmunity and hypoglycemia. Autoantibodies directed against insulin and its receptor. , 1989, Endocrinology and metabolism clinics of North America.

[32]  R N Bergman,et al.  Assessment of insulin sensitivity in vivo. , 1985, Endocrine reviews.

[33]  C. Kahn,et al.  The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. , 1976, The New England journal of medicine.

[34]  A. Krolewski,et al.  Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. , 1990, Annals of internal medicine.

[35]  J. Flier,et al.  Biologic activities of naturally occurring human insulin receptor mutations. Evidence that metabolic effects of insulin can be mediated by a kinase-deficient insulin receptor mutant. , 1991, The Journal of biological chemistry.

[36]  J. Olefsky,et al.  Effects of insulin incubation on insulin binding, glucose transport, and insulin degradation by isolated rat adipocytes. Evidence for hormone-induced desensitization at the receptor and postreceptor level. , 1980, The Journal of clinical investigation.

[37]  D. McClain Insulin Action in Cells Expressing Truncated or Kinase-Defective Insulin Receptors: Dissection of Multiple Hormone-Signaling Pathways , 1990, Diabetes Care.

[38]  C. Bogardus,et al.  Insulin resistance is associated with reduced fasting and insulin-stimulated glycogen synthase phosphatase activity in human skeletal muscle. , 1990, The Journal of clinical investigation.

[39]  Y. Ebina,et al.  Human diabetes associated with a mutation in the tyrosine kinase domain of the insulin receptor , 1989 .

[40]  J. Olefsky,et al.  Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus. , 1988, The Journal of clinical investigation.

[41]  I. Simpson,et al.  Counter-regulation of insulin-stimulated glucose transport by catecholamines in the isolated rat adipose cell. , 1984, The Journal of biological chemistry.

[42]  R G Shulman,et al.  Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. , 1990, The New England journal of medicine.

[43]  G. Lienhard,et al.  Dexamethasone causes translocation of glucose transporters from the plasma membrane to an intracellular site in human fibroblasts. , 1987, The Journal of biological chemistry.

[44]  R. Denton Search for the missing links , 1990, Nature.

[45]  B. Senior,et al.  THE SYNDROMES OF TOTAL LIPODYSTROPHY AND OF PARTIAL LIPODYSTROPHY. , 1964, Pediatrics.

[46]  E. Newsholme,et al.  Effects of analogues of adenosine and methyl xanthines on insulin sensitivity in soleus muscle of the rat , 1984, FEBS letters.

[47]  L. Landsberg,et al.  Hypertension in Obesity and NIDDM: Role of Insulin and Sympathetic Nervous System , 1991, Diabetes Care.

[48]  J. Flier,et al.  Detection of an alteration in the insulin-receptor gene in a patient with insulin resistance, acanthosis nigricans, and the polycystic ovary syndrome (type A insulin resistance). , 1988, The New England journal of medicine.

[49]  R. DeFronzo,et al.  Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression. , 1991, The Journal of clinical investigation.

[50]  R. O’Brien,et al.  PEPCK Gene as Model of Inhibitory Effects of Insulin on Gene Transcription , 1990, Diabetes Care.

[51]  J. Olefsky,et al.  Reversibility of defective adipocyte insulin receptor kinase activity in non-insulin-dependent diabetes mellitus. Effect of weight loss. , 1988, The Journal of clinical investigation.

[52]  C. Kahn,et al.  Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity. , 1988, The Journal of biological chemistry.

[53]  L. Poretsky On the paradox of insulin-induced hyperandrogenism in insulin-resistant states. , 1991, Endocrine reviews.

[54]  Simeon I. Taylor,et al.  Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. , 1988, Science.

[55]  Jerrold,et al.  Insulin resistance and diabetes due to different mutations in the tyrosine kinase domain of both insulin receptor gene alleles. , 1991, The Journal of biological chemistry.

[56]  V. Duronio,et al.  Insulin-like growth factor I receptor beta-subunit heterogeneity. Evidence for hybrid tetramers composed of insulin-like growth factor I and insulin receptor heterodimers. , 1989, The Journal of biological chemistry.

[57]  F. Grigorescu,et al.  Distribution and characterization of insulin and insulin-like growth factor I receptors in normal human ovary. , 1985, The Journal of clinical endocrinology and metabolism.

[58]  G. Dohm,et al.  An in vitro human muscle preparation suitable for metabolic studies. Decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects. , 1988, The Journal of clinical investigation.

[59]  G. J. Sale,et al.  Insulin-receptor phosphotyrosyl-protein phosphatases. , 1988, The Biochemical journal.

[60]  M. Irie,et al.  Glucagon inhibits insulin activation of glucose transport in rat adipocytes mainly through a postbinding process. , 1990, Endocrinology.

[61]  C. Kahn,et al.  Decreased binding of insulin to its receptors in rats with hormone induced insulin resistance. , 1973, Biochemical and biophysical research communications.

[62]  A. Saltiel Second Messengers of Insulin Action , 1990, Diabetes Care.

[63]  H. Häring,et al.  Insulin receptor kinase defects in insulin-resistant tissues and their role in the pathogenesis of NIDDM. , 1989, Diabetes/metabolism reviews.

[64]  R. Henry,et al.  Multiple defects in muscle glycogen synthase activity contribute to reduced glycogen synthesis in non-insulin dependent diabetes mellitus. , 1991, The Journal of clinical investigation.

[65]  Y. Ebina,et al.  Human diabetes associated with a deletion of the tyrosine kinase domain of the insulin receptor. , 1989, Science.

[66]  Y. Ebina,et al.  Insulin-resistant diabetes associated with partial deletion of insulin-receptor gene , 1990, The Lancet.

[67]  J. Olefsky Lilly Lecture 1980: Insulin Resistance and Insulin Action: An In Vitro and In Vivo Perspective , 1981, Diabetes.

[68]  C. Kahn,et al.  Receptors, antireceptor antibodies and mechanisms of insulin resistance. , 1979, The New England journal of medicine.

[69]  Y. Fujita-Yamaguchi,et al.  Nonbinding inhibitory antiinsulin receptor antibodies. A new type of autoantibodies in human diabetes. , 1988, The Journal of clinical investigation.

[70]  A. Dunaif,et al.  Suppression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in the polycystic ovary syndrome. , 1990, The Journal of clinical endocrinology and metabolism.

[71]  M. Rechler,et al.  Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors. , 1978, The New England journal of medicine.

[72]  K. Minaker,et al.  Characterization of the insulin resistance of aging. , 1983, The Journal of clinical investigation.

[73]  J. Flier,et al.  Familial insulin resistance with acanthosis nigricans, acral hypertrophy, and muscle cramps. , 1980, The New England journal of medicine.

[74]  G. Dohm,et al.  Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes. , 1987, The Journal of clinical investigation.

[75]  Simeon I. Taylor,et al.  Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance. , 1990, The Journal of clinical investigation.

[76]  A. Plet,et al.  Leprechaunism: studies of the relationship among hyperinsulinism, insulin resistance, and growth retardation. , 1979, The Journal of clinical endocrinology and metabolism.

[77]  C. Kahn,et al.  Epidermal growth factor receptor defects in leprechaunism. A multiple growth factor-resistant syndrome. , 1989, The Journal of clinical investigation.

[78]  C A Stuart,et al.  Prevalence of acanthosis nigricans in an unselected population. , 1989, The American journal of medicine.

[79]  K. Jarnagin,et al.  The human insulin receptor cDNA: The structural basis for hormone-activated transmembrane signalling , 1985, Cell.

[80]  R. Stout Overview of the association between insulin and atherosclerosis. , 1985, Metabolism: clinical and experimental.

[81]  L. Sandkuyl,et al.  A leucine‐to‐proline mutation in the insulin receptor in a family with insulin resistance. , 1989, The EMBO journal.

[82]  J. Schwartz,et al.  Differential regulation of two glucose transporters by chronic growth hormone treatment of cultured 3T3-F442A adipose cells. , 1990, The Journal of biological chemistry.

[83]  N J Cox,et al.  Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[84]  J. Flier,et al.  A naturally occurring mutation of insulin receptor alanine 1134 impairs tyrosine kinase function and is associated with dominantly inherited insulin resistance. , 1990, The Journal of biological chemistry.

[85]  S. Seino,et al.  Structure of the human insulin receptor gene and characterization of its promoter. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[86]  C. Kahn,et al.  Tyrosine-specific protein kinase activity is associated with the purified insulin receptor. , 1983, Proceedings of the National Academy of Sciences of the United States of America.