Renal gluconeogenesis: its importance in human glucose homeostasis.

Studies conducted over the last 60 years in animals and in vitro have provided considerable evidence that the mammalian kidney can make glucose and release it under various conditions. Until quite recently however, it was generally believed that the human kidney was not an important source of glucose except during acidosis and after prolonged fasting. This review will summarize early work in animals and humans, discuss methodological problems in assessing renal glucose release in vivo, and present results of recent human studies that provide evidence that the kidney may play a significant role in carbohydrate metabolism under both physiological and pathological conditions.

[1]  K. Nair,et al.  Assessment of postabsorptive renal glucose metabolism in humans with multiple glucose tracers. , 2001, Diabetes.

[2]  P. Garlick,et al.  Regulation of splanchnic and renal substrate supply by insulin in humans. , 2000, Metabolism: clinical and experimental.

[3]  N. Heaton,et al.  Renal glucose production compensates for the liver during the anhepatic phase of liver transplantation. , 2000, Diabetes.

[4]  J. Gerich,et al.  Role of the human kidney in glucose counterregulation. , 1999, Diabetes.

[5]  P. Garlick,et al.  Renal glucose production during insulin-induced hypoglycemia in humans. , 1999, Diabetes.

[6]  J. Wahren,et al.  Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting. , 1999, Diabetes.

[7]  P. Garlick,et al.  Insulin regulation of renal glucose metabolism in humans. , 1999, American journal of physiology. Endocrinology and metabolism.

[8]  C Meyer,et al.  Effects of physiological hyperinsulinemia on systemic, renal, and hepatic substrate metabolism. , 1998, The American journal of physiology.

[9]  C Meyer,et al.  Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal postabsorptive humans. , 1998, Metabolism: clinical and experimental.

[10]  M. Stumvoll,et al.  Abnormal renal and hepatic glucose metabolism in type 2 diabetes mellitus. , 1998, The Journal of clinical investigation.

[11]  M. Stumvoll,et al.  Human kidney and liver gluconeogenesis: evidence for organ substrate selectivity. , 1998, American journal of physiology. Endocrinology and metabolism.

[12]  J. Wahren,et al.  Quantifying gluconeogenesis during fasting. , 1997, The American journal of physiology.

[13]  C Meyer,et al.  Human kidney free fatty acid and glucose uptake: evidence for a renal glucose-fatty acid cycle. , 1997, The American journal of physiology.

[14]  S. Turner,et al.  Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. , 1997, The Journal of clinical investigation.

[15]  M. Vranic,et al.  Fatty Acids Mediate the Acute Extrahepatic Effects of Insulin on Hepatic Glucose Production in Humans , 1997, Diabetes.

[16]  M. Stumvoll,et al.  Renal glucose production and utilization: new aspects in humans , 1997, Diabetologia.

[17]  G. Mithieux,et al.  Glucose-6-Phosphatase mRNA and Activity Are Increased to the Same Extent in Kidney and Liver of Diabetic Rats , 1996, Diabetes.

[18]  D L Rothman,et al.  Contribution of net hepatic glycogenolysis to glucose production during the early postprandial period. , 1996, The American journal of physiology.

[19]  M. Stumvoll,et al.  Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine. , 1995, The Journal of clinical investigation.

[20]  J. Wahren,et al.  Use of 2H2O for estimating rates of gluconeogenesis. Application to the fasted state. , 1995, The Journal of clinical investigation.

[21]  J. Wahren,et al.  Renal oxygen consumption, thermogenesis, and amino acid utilization during i.v. infusion of amino acids in man. , 1994, The American journal of physiology.

[22]  R. Judd,et al.  Insulin regulation of renal glucose metabolism in conscious dogs. , 1994, The Journal of clinical investigation.

[23]  O. McGuinness,et al.  Impact of chronic stress hormone infusion on hepatic carbohydrate metabolism in the conscious dog. , 1993, The American journal of physiology.

[24]  J. Gerich,et al.  Control of glycaemia. , 1993, Bailliere's clinical endocrinology and metabolism.

[25]  A. Sollevi,et al.  Splanchnic and renal vasoconstrictor and metabolic responses to neuropeptide Y in resting and exercising man. , 1992, Acta physiologica Scandinavica.

[26]  R. Bergman,et al.  Peripheral effects of insulin dominate suppression of fasting hepatic glucose production. , 1990, The American journal of physiology.

[27]  B. Nyberg,et al.  Gut Exchange of Glucose and Lactate in Basal State and After Oral Glucose Ingestion in Postoperative Patients , 1990, Diabetes.

[28]  R. Arem Hypoglycemia associated with renal failure. , 1989, Endocrinology and metabolism clinics of North America.

[29]  P. Felig,et al.  Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls. , 1989, The Journal of clinical investigation.

[30]  J. Gerich,et al.  Glucose Counterregulation and Its Impact on Diabetes Mellitus , 1988, Diabetes.

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

[32]  G Sonnenberg,et al.  Skeletal muscle glycolysis, oxidation, and storage of an oral glucose load. , 1988, The Journal of clinical investigation.

[33]  A. Schoolwerth,et al.  Renal gluconeogenesis. , 1988, Mineral and electrolyte metabolism.

[34]  R. DeFronzo Use of the splanchnic/hepatic balance technique in the study of glucose metabolism. , 1987, Bailliere's clinical endocrinology and metabolism.

[35]  W. Guder,et al.  Renal substrate metabolism. , 1986, Physiological reviews.

[36]  R. DeFronzo,et al.  Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. , 1985, The Journal of clinical investigation.

[37]  W. Guder,et al.  Enzyme distribution along the nephron. , 1984, Kidney international.

[38]  P. Fournel,et al.  Renal enzymes during experimental diabetes mellitus in the rat. Role of insulin, carbohydrate metabolism, and ketoacidosis. , 1984, Canadian journal of physiology and pharmacology.

[39]  P. Felig,et al.  Role of the Kidney in the Metabolism of Fructose in 60-hour Fasted Humans , 1982, Diabetes.

[40]  T. Kreulen,et al.  Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis. , 1981, The Journal of clinical investigation.

[41]  S. Welle,et al.  Increased plasma norepinephrine concentrations and metabolic rates following glucose ingestion in man. , 1980, Metabolism: clinical and experimental.

[42]  P. Felig,et al.  The Contrasting Responses of Splanchnic and Renal Glucose Output to Gluconeogenic Substrates and to Hypoglucagonemia in 60-h-fasted Humans , 1980, Diabetes.

[43]  G. Garibotto,et al.  Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency. , 1980, The Journal of clinical investigation.

[44]  P. Ferré,et al.  Interactions in vivo between oxidation of non-esterified fatty acids and gluconeogenesis in the newborn rat. , 1979, The Biochemical journal.

[45]  G. Garibotto,et al.  Effects of chronic renal insufficiency and metabolic acidosis on glutamine metabolism in man. , 1978, Clinical science and molecular medicine.

[46]  P. Felig,et al.  Influence of Maturity-onset Diabetes on Splanchnic Glucose Balance After Oral Glucose Ingestion , 1978, Diabetes.

[47]  P. Felig,et al.  Renal Substrate Exchange in Human Diabetes Mellitus , 1975, Diabetes.

[48]  J. German,et al.  MONGOLISM BY TERTIARY TRISOMY , 1975, The Lancet.

[49]  P. Felig,et al.  Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids. , 1974, The Journal of clinical investigation.

[50]  P. Felig,et al.  Splanchnic glucose and amino acid metabolism in obesity. , 1974, The Journal of clinical investigation.

[51]  E. Cerasi,et al.  Splanchnic and peripheral glucose and amino acid metabolism in diabetes mellitus. , 1972, The Journal of clinical investigation.

[52]  G F Cahill,et al.  Starvation in man. , 1970, The New England journal of medicine.

[53]  P. Felig,et al.  Liver and kidney metabolism during prolonged starvation. , 1969, The Journal of clinical investigation.

[54]  A. Svanborg,et al.  Arterio-hepatic venous differences of free fatty acids and amino acids. Studies in patients with diabetes or essential hypercholesterolemia, and in healthy individuals. , 2009, Acta medica Scandinavica.

[55]  N. Stamm,et al.  Regulation of gluconeogenesis and glycolysis: studies of mechanisms controlling enzyme activity. , 1967, Advances in enzyme regulation.

[56]  E. Housley,et al.  Gluconeogenesis by the Human Kidney , 1966, Nature.

[57]  P. Schollmeyer,et al.  Substrate-utilization of the Human Kidney , 1966, Nature.

[58]  M. West,et al.  Ultrastructural observations on renal glycogen in normal and pathologic human kidneys. , 1966, Laboratory investigation; a journal of technical methods and pathology.

[59]  H. Krebs,et al.  ACCELERATION OF RENAL GLUCONEOGENESIS BY KETONE BODIES AND FATTY ACIDS. , 1965, The Biochemical journal.

[60]  H. Krebs The Croonian Lecture, 1963 Gluconeogenesis , 1964, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[61]  H. Krebs,et al.  RENAL GLUCONEOGENESIS. 2. THE GLUCONEOGENIC CAPACITY OF THE KIDNEY CORTEX OF VARIOUS SPECIES. , 1963, The Biochemical journal.

[62]  R. R. Robinson,et al.  Amino acid extraction and ammonia metabolism by the human kidney during the prolonged administration of ammonium chloride. , 1963, The Journal of clinical investigation.

[63]  D. A. Bennett,et al.  Renal gluconeogenesis. The effect of diet on the gluconeogenic capacity of rat-kidney-cortex slices. , 1963, The Biochemical journal.

[64]  H. Krebs,et al.  RENAL GLUCONEOGENESIS. IV. GLUCONEOGENESIS FROM SUBSTRATE COMBINATIONS. , 1963, Acta biologica et medica Germanica.

[65]  Seymour Geisser,et al.  Statistical Principles in Experimental Design , 1963 .

[66]  B. Landau Gluconeogenesis and pyruvate metabolism in rat kidney, in vitro. , 1960, Endocrinology.

[67]  C. Teng Studies on carbohydrate metabolism in rat kidney slices. II. Effect of alloxan diabetes and insulin administration on glucose uptake and glucose formation. , 1954, Archives of biochemistry and biophysics.

[68]  H. Zimmerman,et al.  Fasting blood sugar in hepatic disease with reference to infrequency of hypoglycemia. , 1953, A.M.A. archives of internal medicine.

[69]  B. Billing,et al.  Hepatic glucose output and hepatic insulin sensitivity in diabetes mellitus. , 1951, Lancet.

[70]  C. Brun A rapid method for the determination of para-aminohippuric acid in kidney function tests. , 1951, The Journal of laboratory and clinical medicine.

[71]  A. N. Wick,et al.  Formation of glucose by the kidney. , 1950, The American journal of physiology.

[72]  J. J. Curry,et al.  THE ESTIMATION OF HEPATIC BLOOD FLOW IN MAN. , 1945, The Journal of clinical investigation.

[73]  R. M. Reinecke THE KIDNEY AS A SOURCE OF GLUCOSE IN THE EVISCERATED RAT , 1943 .

[74]  H. Bergman,et al.  THE RELATIONSHIP OF KIDNEY FUNCTION TO THE GLUCOSE UTILIZATION OF THE EXTRA ABDOMINAL TISSUES , 1938 .