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 To accomplish this, glucose was infused into conscious dogs whose basal insulin and glucagon secretion had been replaced by exogenous intraportal insulin and glucagon infusion after somatostatin inhibition of endogenous pancreatic hormone release. The acute induction of hyperglycemia (mean increment of 121 mg/dl) in the presence of basal levels of insulin (7±1 μU/ml) and glucagon (76±3 pg/ml) resulted in a 56% decrease in net hepatic glucose production but did not cause net hepatic glucose uptake.
Gerald I. Shulman, John E. Liljenquist, Phillip E. Williams, William W. Lacy, Alan D. Cherrington
Title and authors | Publication | Year |
---|---|---|
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Current Diabetes Reports | 2019 |
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Current Diabetes Reports | 2015 |
Comprehensive Physiology
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Comprehensive Physiology | 2014 |
The regulation of glucose metabolism: implications and considerations for the assessment of glucose homeostasis in rodents
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American journal of physiology. Endocrinology and metabolism | 2014 |
Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover
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Journal of Clinical Investigation | 2012 |
Fetal and Neonatal Physiology
LH Johnson, VK Bhutani |
Fetal and Neonatal Physiology | 2011 |
Effects of prior exercise on insulin-mediated and noninsulin-mediated glucose uptake in horses during a hyperglycaemic clamp
RJ Geor, L Stewart-Hunt, LJ McCUTCHEON |
Equine Veterinary Journal | 2010 |
Regulation of net hepatic glycogenolysis and gluconeogenesis by epinephrine in humans
S Dufour, V Lebon, GI Shulman, KF Petersen |
American journal of physiology. Endocrinology and metabolism | 2009 |
Regulation of net hepatic glycogenolysis and gluconeogenesis by epinephrine in humans
S Dufour, V Lebon, GI Shulman, KF Petersen |
American journal of physiology. Endocrinology and metabolism | 2009 |
Splanchnic Regulation of Glucose Production
J Wahren, K Ekberg |
Annual Review of Nutrition | 2007 |
Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony
MA Herman, BB Kahn |
Journal of Clinical Investigation | 2006 |
International Textbook of Diabetes Mellitus
RA DeFronzo, L Mandarino, E Ferrannini |
International Textbook of Diabetes Mellitus | 2003 |
Regulation of hepatic and peripheral glucose disposal
MC Moore, AD Cherrington, DH Wasserman |
Best Practice & Research Clinical Endocrinology & Metabolism | 2003 |
Effect of 5-Aminoimidazole-4-Carboxamide-1- -D-Ribofuranoside Infusion on In Vivo Glucose and Lipid Metabolism in Lean and Obese Zucker Rats
R Bergeron, SF Previs, GW Cline, P Perret, RR Russell, LH Young, GI Shulman |
Diabetes | 2001 |
Loss of Insulin Signaling in Hepatocytes Leads to Severe Insulin Resistance and Progressive Hepatic Dysfunction
MD Michael, RN Kulkarni, C Postic, SF Previs, GI Shulman, MA Magnuson, CR Kahn |
Molecular Cell | 2000 |
Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man
M Dirlewanger, PH Schneiter, N Paquot, E Jequier, V Rey, L Tappy |
Clinical Nutrition | 2000 |
Banting Lecture 1997. Control of glucose uptake and release by the liver in vivo
L Rossetti, A Giaccari, N Barzilai, K Howard, G Sebel, M Hu |
Journal of Clinical Investigation | 1999 |
Autoregulation of glucose production in health and disease
L Tappy, R Chioléro, M Berger |
Current Opinion in Clinical Nutrition and Metabolic Care | 1999 |
Banting Lecture 1997. Control of glucose uptake and release by the liver in vivo
L Rossetti, A Giaccari, N Barzilai, K Howard, G Sebel, M Hu |
Diabetes | 1999 |
Regulation of endogenous glucose production by glucose per se is impaired in type 2 diabetes mellitus
M Mevorach, A Giacca, Y Aharon, M Hawkins, H Shamoon, L Rossetti |
Journal of Clinical Investigation | 1998 |
Mechanism by which glucose and insulin inhibit net hepatic glycogenolysis in humans
KF Petersen, D Laurent, DL Rothman, GW Cline, GI Shulman |
Journal of Clinical Investigation | 1998 |
Carbon Flux via the Pentose Phosphate Pathway Regulates the Hepatic Expression of the Glucose-6-phosphatase and Phosphoenolpyruvate Carboxykinase Genes in Conscious Rats
D Massillon, W Chen, N Barzilai, D Prus-Wertheimer, M Hawkins, R Liu, R Taub, L Rossetti |
The Journal of biological chemistry | 1998 |
Physiological changes in circulating glucagon alter hepatic glucose disposition during portal glucose delivery
LC Holste, CC Connolly, MC Moore, DW Neal, AD Cherrington |
American journal of physiology. Endocrinology and metabolism | 1997 |
Abnormal regulation of HGP by hyperglycemia in mice with a disrupted glucokinase allele
L Rossetti, W Chen, M Hu, M Hawkins, N Barzilai, S Efrat |
American journal of physiology. Endocrinology and metabolism | 1997 |
The roles of insulin and glucagon in the regulation of hepatic glycogen synthesis and turnover in humans
M Roden, G Perseghin, KF Petersen, JH Hwang, GW Cline, K Gerow, DL Rothman, GI Shulman |
Journal of Clinical Investigation | 1996 |
Impact of infection on hepatic disposal of a peripheral glucose infusion in the conscious dog
OP McGuinness, J Jacobs, C Moran, B Lacy |
American journal of physiology. Endocrinology and metabolism | 1995 |
Quantitation of hepatic glucose fluxes and pathways of hepatic glycogen synthesis in conscious mice
D Massillon, W Chen, M Hawkins, R Liu, N Barzilai, L Rossetti |
American journal of physiology. Endocrinology and metabolism | 1995 |
Pulsatility does not alter the response to a physiological increment in glucagon in the conscious dog
RL Dobbins, SN Davis, DW Neal, C Cobelli, AD Cherrington |
American journal of physiology. Endocrinology and metabolism | 1994 |
Effect of hepatic nerves on disposition of an intraduodenal glucose load
MC Moore, GI Shulman, A Giaccari, MJ Pagliassotti, G Cline, D Neal, L Rossetti, AD Cherrington |
American journal of physiology. Endocrinology and metabolism | 1993 |
Surgical alterations of the pancreas and insulin-independent glucose disposal
DA Krusch, TL Pruett, G Cornett, JB Hanks |
Journal of Surgical Research | 1992 |
BASREP: a method for maintaining euglycemia during somatostatin suppression of pancreatic secretion
G Pacini, M Ader, RN Bergman |
Computer Methods and Programs in Biomedicine | 1992 |
Role of hepatic nerves in response of liver to intraportal glucose delivery in dogs
B Adkins-Marshall, MJ Pagliassotti, JR Asher, CC Connolly, DW Neal, PE Williams, SR Myers, GK Hendrick, RB Adkins, AD Cherrington |
American journal of physiology. Endocrinology and metabolism | 1992 |
Restoration of stable metabolic conditions during islet suppression in dogs
DC Bradley, RN Bergman |
American journal of physiology. Endocrinology and metabolism | 1992 |
Short-term regulation of insulin-mediated glucose utilization in four-day fasted human volunteers: role of amino acid availability
PJ Flakoll, LS Wentzel, DE Rice, JO Hill, NN Abumrad |
Diabetologia | 1992 |
Intraportal glucose delivery alters the relationship between net hepatic glucose uptake and the insulin concentration
SR Myers, OP McGuinness, DW Neal, AD Cherrington |
Journal of Clinical Investigation | 1991 |
Intraportal glucose delivery enhances the effects of hepatic glucose load on net hepatic glucose uptake in vivo
SR Myers, DW Biggers, DW Neal, AD Cherrington |
Journal of Clinical Investigation | 1991 |
Effects of small changes in glucagon on glucose production during a euglycemic, hyperinsulinemic clamp
SR Myers, MP Diamond, BA Adkins-Marshall, PE Williams, R Stinsen, AD Cherrington |
Metabolism | 1991 |
Mechanism of growth hormone-induced postprandial carbohydrate intolerance in humans
P Butler, E Kryshak, R Rizza |
American journal of physiology. Endocrinology and metabolism | 1991 |
Amino Acids Enhance Insulin Resistance to Exogenous Glucose Infusion in Overnight-Fasted Humans
PJ Flakoll, M Kulaylat, M Frexes-Steed, JO Hill, NN Abumrad |
JPEN. Journal of parenteral and enteral nutrition | 1991 |
Fuel Homeostasis and the Nervous System
M Vranic, S Efendic, CH Hollenberg |
1991 | |
Evidence that hyperglycaemia per se does not inhibit hepatic glucose production in man
MJ Mller, KJ Acheson, AG Burger, E Jequier |
European Journal of Applied Physiology and Occupational Physiology | 1990 |
Intravenous and subcutaneous administration of a long-acting somatostatin analogue: effects on glucose metabolism and splanchnic haemodynamics in healthy subjects
LS Eriksson, J Wahren |
European Journal of Clinical Investigation | 1989 |
Influence of the route of glucose administration on hepatic glycogen repletion
GI Shulman, L Rossetti |
American journal of physiology. Endocrinology and metabolism | 1989 |
Escape of hepatic glucose production during hyperglycemic clamp
D Elahi, GS Meneilly, KL Minaker, DK Andersen, JW Rowe |
American journal of physiology. Endocrinology and metabolism | 1989 |
Review: Parenteral Nutrition in Patients with Diabetes Mellitus: Theoretical and Practical Considerations
M Mcmahon, N Manji, DF Driscoll, BR Bistrian |
JPEN. Journal of parenteral and enteral nutrition | 1989 |
Regulation of Carbohydrate Metabolism and Response to Hypoglycemia
PC Butler, RA Rizza |
Endocrinology and metabolism clinics of North America | 1989 |
Effect of chronic intracerebroventricular morphine to feeding responses in male rats
RK Dhatt, AK Rattan, HK Mangat |
Physiology & Behavior | 1988 |
Regulation of hepatic glucose output by glucose in vivo
MJ Müller, J Möring, HJ Seitz |
Metabolism | 1988 |
Effect of alanine concentration independent of changes in insulin and glucagon on alanine and glucose homeostasis in the conscious dog
MP Diamond, RC Rollings, KE Steiner, PE Williams, WW Lacy, AD Cherrington |
Metabolism | 1988 |
Drugs, Athletes, and Physical Performance
JA Thomas |
1988 | |
Importance of the route of intravenous glucose delivery to hepatic glucose balance in the conscious dog
BA Adkins, SR Myers, GK Hendrick, RW Stevenson, PE Williams, AD Cherrington |
Journal of Clinical Investigation | 1987 |
Role of counterregulatory hormones in the regulation of hepatic glucose metabolism
L Saccà |
Diabetes / Metabolism Reviews | 1987 |
Insulin, glucagon, and glucose as regulators of hepatic glucose uptake and production in vivo
AD Cherrington, RW Stevenson, KE Steiner, MA Davis, SR Myers, BA Adkins, NN Abumrad, PE Williams |
Diabetes / Metabolism Reviews | 1987 |
Lack of effect of somatostatin on epinephrine-stimulated glucose production in the dog
RW Stevenson, KE Steiner, PE Williams, AD Cherrington |
Metabolism | 1987 |
Hepatic response to insulin in control of glucose kinetics in the neonatal lamb
RM Cowett, D Tenenbaum |
Metabolism | 1987 |
Basal glucose homeostasis with and without fixed concentrations of glucagon and insulin
RA Jackson, JB Hamling, BM Sim, PM Blix, JB Jaspan, S Markanday, JD Nabarro |
Metabolism | 1987 |
Net hepatic lactate balance following mixed meal feeding in the four-day fasted conscious dog
MA Davis, PE Williams, AD Cherrington |
Metabolism | 1987 |
Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs
RW Stevenson, KE Steiner, GK Hendrick, AD Cherrington |
American journal of physiology. Endocrinology and metabolism | 1987 |
Selective suppression of hepatic glucose output by human proinsulin in the dog
M Lavelle-Jones, MH Scott, O Kolterman, AH Rubenstein, JM Olefsky, AR Moossa |
American journal of physiology. Endocrinology and metabolism | 1987 |
Effects of alpha and beta adrenergic blockade on hepatic glucose balance before and after oral glucose. Role of insulin and glucagon
Z Chap, T Ishida, J Chou, L Michael, C Hartley, M Entman, JB Field |
Journal of Clinical Investigation | 1986 |
The glucose paradox: new perspectives on hepatic carbohydrate metabolism
J Katz, M Kuwajima, DW Foster, JD McGarry |
Trends in Biochemical Sciences | 1986 |
Glucoregulation in alloxan-diabetic dogs
B Lussier, M Vranic, N Kovacevic, G Hetenyi |
Metabolism | 1986 |
Role of hepatic autoregulation in defense against hypoglycemia in humans
G Bolli, PD Feo, G Perriello, SD Cosmo, M Ventura, P Campbell, P Brunetti, JE Gerich |
Journal of Clinical Investigation | 1985 |
Pathophysiology, diagnosis, and management of glucose homeostasis in the neonate
RM Cowett |
Current Problems in Pediatrics | 1985 |
Glucose Counterregulation, Hypoglycemia, and Intensive Insulin Therapy in Diabetes Mellitus
FH Epstein, PE Cryer, JE Gerich |
New England Journal of Medicine | 1985 |
Endocrine Function in the Critically III
S Teich, S Sharpe, B Chernow |
1985 | |
Effects of morphine on glucose homeostasis in the conscious dog
PM Radosevich, PE Williams, DB Lacy, JR McRae, KE Steiner, AD Cherrington, WW Lacy, NN Abumrad |
Journal of Clinical Investigation | 1984 |
Extrapancreatic effect of somatostatin infusion to increase glucose clearance
RN Bergman, M Ader, DT Finegood, G Pacini |
American journal of physiology. Endocrinology and metabolism | 1984 |
Catecholamine responses and their interactions with other glucoregulatory hormones
M Vranic, C Gauthier, D Bilinski, D Wasserman, KE Tayeb, G Hetenyi, HL Lickley |
American journal of physiology. Endocrinology and metabolism | 1984 |
Roles of glucagon and epinephrine in hypoglycemic and nonhypoglycemic glucose counterregulation in humans
PE Cryer, TF Tse, WE Clutter, SD Shah |
American journal of physiology. Endocrinology and metabolism | 1984 |
Neuroendocrine responses to glucose ingestion in man. Specificity, temporal relationships, and quantitative aspects
TF Tse, WE Clutter, SD Shah, JP Miller, PE Cryer |
Journal of Clinical Investigation | 1983 |
Effects of insulin and glucose on the production and utilization of glucose in sheep (Ovis aries)
RP Brockman |
Comparative Biochemistry and Physiology Part A: Physiology | 1983 |
The effect of hyperglycaemia on the rates of appearance and metabolic clearance of glucose in sheep (Ovis aries)
RP Brockman |
Comparative Biochemistry and Physiology Part A: Physiology | 1983 |
Glucagon I
PJ Lefèbvre |
1983 | |
Studies on the mechanism by which exogenous glucose is converted into liver glycogen in the rat. A direct or an indirect pathway?
CB Newgard, LJ Hirsch, DW Foster, JD McGarry |
The Journal of biological chemistry | 1983 |
Differential effects of insulin on splanchnic and peripheral glucose disposal after an intravenous glucose load in man
L Saccà, M Cicala, B Trimarco, B Ungaro, C Vigorito |
Journal of Clinical Investigation | 1982 |
Insulin increases the maximum velocity for glucose uptake without altering the Michaelis constant in man. Evidence that insulin increases glucose uptake merely by providing additional transport sites
I Gottesman, L Mandarino, C Verdonk, R Rizza, J Gerich |
Journal of Clinical Investigation | 1982 |
2 The effects of insulin on carbohydrate metabolism in vivo
AD Cherrington, KE Steiner |
Clinics in Endocrinology and Metabolism | 1982 |
Mechanisms of epinephrine-induced glucose intolerance in normal humans
L Saccà, C Vigorito, M Cicala, B Ungaro, R S Sherwin |
Journal of Clinical Investigation | 1982 |
Mechanisms of Epinephrine-induced Glucose Intolerance in Normal Humans
L Saccà, C Vigorito, M Cicala, B Ungaro, RS Sherwin |
Journal of Clinical Investigation | 1982 |
Cyclic Nucleotides
JW Kebabian, JA Nathanson |
1982 | |
Influence of abdominal surgical trauma and intraoperative infusion of glucose on splanchnic glucose metabolism in man
H Stjernström, L Jorfeldt, L Wiklund |
Clinical Physiology | 1981 |
Autoregulation by glucose of hepatic glucose balance: Permissive effect of insulin
MB Davidson |
Metabolism | 1981 |
The glucoregulatory response to intravenous glucose infusion in normal man: Roles of insulin and glucose
L Saccà, D Vitale, M Cicala, B Trimarco, B Ungaro |
Metabolism | 1981 |
Glucagon and the a Cell: Physiology and Pathophysiology(First of Two Parts)
RH Unger, L Orci |
New England Journal of Medicine | 1981 |
Glucoregulatory and metabolic response to exercise in obese noninsulin-dependent diabetes
HL Minuk, M Vranic, EB Marliss, AK Hanna, AM Albisser, B Zinman |
American journal of physiology. Endocrinology and metabolism | 1981 |
Effect of counterregulatory hormones on kinetic response to ingested glucose in dogs
L Sacca, M Cicala, G Corso, B Ungaro, RS Sherwin |
American journal of physiology. Endocrinology and metabolism | 1981 |
Effect of glucose, independent of changes in insulin and glucagon secretion, on alanine metabolism in the conscious dog
GI Shulman, WW Lacy, JE Liljenquist, U Keller, PE Williams, AD Cherrington |
Journal of Clinical Investigation | 1980 |
Progress in Hormone Biochemistry and Pharmacology
M Briggs, A Corbin |
1980 | |
Influence of Continuous Physiologic Hyperinsulinemia on Glucose Kinetics and Counterregulatory Hormones in Normal and Diabetic Humans
L Saccà, R Sherwin, R Hendler, P Felig |
Journal of Clinical Investigation | 1979 |
Importance of hypoglycemia-induced glucose production during isolated glucagon deficiency
AD Cherrington, JE Liljenquist, GI Shulman, PE Williams, WW Lacy |
American journal of physiology. Endocrinology and metabolism | 1979 |
Possible mechanism by which somatostatin-induced glucagon suppression improves glucose tolerance during insulinopaenia in man
JE Liljenquist, ZT Bloomgarden, AD Cherrington, JM Perry, D Rabin |
Diabetologia | 1979 |
Contemporary Metabolism
N Freinkel |
1979 | |
Advances in Metabolic Disorders
G Aurbach, JT Potts |
Advances in Metabolic Disorders | 1964 |