Reviewed are data on gluconeogenesis (GNG) and glycogenolysis (GL) obtained in healthy volunteers and diabetic patients with newer, quantitative methods. Specifically addressed are effects of overnight and prolonged fasting, of acute changes in serum insulin and plasma free fatty acid (FFA) levels, as well as acute changes of combined FFA and insulin levels on GNG and GL in nondiabetic subjects and of abnormalities in GNG and GL in patients with type 1 and type 2 diabetes.
StumvollM., ChintalapudiU., PerrielloG.Uptake and release of glucose by the human kidney: postabsorptive rates and responses to epinephrine.J Clin Invest1995; 96: 2528–33.
2.
CahillG.F.Jr.Starvation in man.N Engl J Med1970; 282: 668–75.
3.
DeFronzoR.A., FerranniniE., SimonsonD.C.Fasting hyperglycemia in non-insulin-dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake.Metabolism1989; 38: 387–95.
4.
KatzJ.Determination of gluconeogenesis in vivo with 14C-labeled substrates.Am J Physiol Regul Integr Comp Physiol1985; 248: R391–9.
5.
RothmanD.L., MagnussonI., KatzL.D.Quantitation of hepatic glycogenosis and gluconeogenesis in fasting humans with 13C NMR.Science1991; 254: 573–6.
6.
HellersteinM.K., NeeseR.A., LinfootP.Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study.J Clin Invest1997; 100: 1305–19.
7.
KatzJ., TayekJ.A.Gluconeogenesis and the Cori cycle in 12-, 20-, and 40-h-fasted humans.Am J Physiol1998: 275: E537–42.
8.
LandauB.R., WahrenJ., ChandramouliV.Contributions of gluconeogenesis to glucose production in the fasted state.J Clin Invest1996; 98: 378–85.
9.
LandauB.R.Methods for measuring glycogen cycling.Am J Physiol2001; 281: E413.
10.
ChenX., IqbalN., BodenG.The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects.J Clin Invest1999; 103: 365–72.
11.
GastaldelliA., ToschiE., PettitiM.Effect of physiological hyperinsulinemia on gluconeogenesis in nondiabetic subjects and in type 2 diabetic patients.Diabetes2001; 50: 1807–12.
12.
BodenG., CheungP., SteinT.P.FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis.Am J Physiol2002; 283: E12–9.
13.
EdgertonD.S., CarinS., EmshwillerM.Small increases in insulin inhibit hepatic glucose production solely caused by an effect of glycogen metabolism.Diabetes2001; 50: 1872–82.
14.
HansonR.W., ReshefL.Regulation of phosphoe/?o/pyruvate carboxykinase mRNA in rat liver and kidney: effects of insulin and cyclic AMP.Annu Rev Biochem1997; 66: 581–611.
15.
Jomain-BaumM., HansonR.W.Regulation of hepatic gluconeogenesis in the guinea pig by fatty acids and ammonia.J Biol Chem1975; 250: 8978–85.
16.
BodenG., JadaliF.Effects of lipid on basal carbohydrate metabolism in normal men.Diabetes1991; 40: 686–92.
17.
RodenM., StinglH., ChandramouliV.Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in humans.Diabetes2000; 49: 701–7.
18.
CloreJ.N., GlickmanP.S., NestlerJ.E., BlackardW.G.In vivo evidence for hepatic autoregulation during FFA-stimulated gluconeogenesis in normal humans.Am J Physiol1991; 261: E524–9.
19.
FanelliC., CalderoneS., EpifanoL.Demonstration of a critical role for free fatty acids in mediating counterregula-tory stimulation of gluconeogenesis and suppression of glucose utilization in humans.J Clin Invest1993; 92: 1617–22.
20.
JensenT., NurjhanN., ConsoliA., GerichJ.E.Failure of substrate-induced gluconeogenesis to increase overall glucose appearance in normal humans: demonstration of hepatic autoregulation without a change in plasma glucose concentration.J Clin Invest1990; 86: 489–97.
21.
BevilacquaS., BuzzigoliG., BonadonnaR.Operation of Randies cycle in patients with NIDDM.Diabetes1990; 39: 383–9.
22.
BodenG., ChenX., RuizJ.Mechanisms of fatty acid-induced inhibition of glucose uptake.J Clin Invest1994; 93: 2438–46.
23.
FerranniniE., BarrettE., BevilacquaS., DeFronzoR.Effect of fatty acids on glucose production and utilization in man.J Clin Invest1983; 72: 1737–47.
24.
SalorantaC., KoivistoV., WidenE.Contribution of muscle and liver to glucose-fatty acid cycle in humans.Am I Physiol1993; 264: E599–605.
25.
ShahP., VellaA., BasuA.Effects of free fatty acids and glycerol on splanchnic glucose metabolism and insulin extraction in nondiabetic humans.Diabetes2002; 51: 301–10.
26.
MagnussonI., RothmanD.L., KatzL.D.Increased rate of gluconeogenesis in type II diabetes mellitus.J Clin Invest1992; 90: 1323–7.
27.
WajngotA., ChandramouliV., SchumannW.C.Quantitative contributions of gluconeogenesis to glucose production during fasting in type 2 diabetes mellitus.Metabolism2001; 50: 47–52.
28.
BodenG., ChenX., SteinT.P.Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus.Am J Physiol2001; 280: E23–30.
29.
ChenY.D.I., JengC.Y., HollenbeckC.B.Relationship between plasma glucose and insulin concentration, glucose production, and glucose disposal in normal subjects and patients with non-insulin-dependent diabetes.J Clin Invest1988; 82: 21–5.
30.
BodenG., ChenX., CapulongE., MozzoliM.Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes.Diabetes2001; 50: 810–6.
31.
BodenG., CheungP., HomkoC.Effects of acute insulin excess and deficiency on gluconeogenesis and glycogenosis in type 1 diabetes.Diabetes2003; 52: 133–7.
