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K F Petersen

Publications and source records attributed to K F Petersen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mechanism by which glucose and insulin inhibit net hepatic glycogenolysis in humans.

13C NMR spectroscopy was used to assess flux rates of hepatic glycogen synthase and phosphorylase in overnight-fasted subjects under one of four hypoglucagonemic conditions: protocol I, hyperglycemic (approximately 10 mM) -hypoinsulinemia (approximately 40 pM); protocol II, euglycemic (approximately 5 mM) -hyperinsulinemia (approximately 400 pM); protocol III, hyperglycemic (approximately 10 mM) -hyperinsulinemia (approximately 400 pM); and protocol IV; euglycemic (approximately 5 mM) -hypoinsulinemia (approximately 40 pM). Inhibition of net hepatic glycogenolysis occurred in both protocols I and II compared to protocol IV but via a different mechanism. Inhibition of net hepatic glycogenolysis occurred in protocol I mostly due to decreased glycogen phosphorylase flux, whereas in protocol II inhibition of net hepatic glycogenolysis occurred exclusively through the activation of glycogen synthase flux. Phosphorylase flux was unaltered, resulting in extensive glycogen cycling. Relatively high rates of net hepatic glycogen synthesis were observed in protocol III due to combined stimulation of glycogen synthase flux and inhibition of glycogen phosphorylase flux. In conclusion, under hypoglucagonemic conditions: (a) hyperglycemia, per se, inhibits net hepatic glycogenolysis primarily through inhibition of glycogen phosphorylase flux; (b) hyperinsulinemia, per se, inhibits net hepatic glycogenolysis primarily through stimulation of glycogen synthase flux; (c) inhibition of glycogen phosphorylase and the activation of glycogen synthase are not necessarily coupled and coordinated in a reciprocal fashion; and (d) promotion of hepatic glycogen cycling may be the principal mechanism by which insulin inhibits net hepatic glycogenolysis and endogenous glucose production in humans under euglycemic conditions.

Adult↗
PubMed1998

Effect of epinephrine on muscle glycogenolysis and insulin-stimulated muscle glycogen synthesis in humans.

To examine the effects of a physiological increase in plasma epinephrine concentration (approximately 800 pg/ml) on muscle glycogenolysis and insulin-stimulated glycogenesis, we infused epinephrine [1.2 micrograms.(m2 body surface)-1.min-1] for 2 h and monitored muscle glycogen and glucose 6-phosphate (G-6-P) concentrations with 13C/31P nuclear magnetic resonance (NMR) spectroscopy. Epinephrine caused an increase in plasma glucose (delta approximately 50 mg/dl), lactate (delta approximately 1.4 mM), free fatty acids (delta approximately 1,200 microM at peak), and whole body glucose oxidation (delta approximately 0.85 mg.kg-1.min-1) compared with levels in a group of control subjects (n = 4) in the presence of slight hyperinsulinemia (approximately 13 microU/ml, n = 8) or basal insulin (approximately 7 microU/ml, n = 7). However, epinephrine did not induce any detectable changes in glycogen or G-6-P concentrations, whereas muscle inorganic phosphate (Pi) decreased by 35%. Epinephrine infusion during a euglycemic-hyperinsulinemic clamp (n = 8) caused a 45% decrease in the glucose infusion rate that could be mostly attributed to a 73% decrease in muscle glycogen synthesis rate. After an initial increase to approximately 160% of basal values, G-6-P levels decreased by approximately 30% with initiation of the epinephrine infusion. We conclude that a physiological increase in plasma epinephrine concentration 1) has a negligible effect on muscle glycogenolysis at rest, 2) decreases muscle Pi, which may maintain phosphorylase activity at a low level, and 3) causes a major impairment in insulin-stimulated muscle glycogen synthesis, possibly due to inhibition of glucose transport-phosphorylation activity.

Adult↗
PubMed1998

13C/31P NMR studies on the mechanism of insulin resistance in obesity.

The mechanism of insulin resistance in obesity was examined in ten obese (BMI 33 +/- 1 kg/m2) and nine lean (BMI 22 +/- 1 kg/m2) Caucasian women during a hyperglycemic-hyperinsulinemic clamp using 13C and 31P nuclear magnetic resonance (NMR) spectroscopy to measure rates of muscle glycogen synthesis and intramuscular glucose-6-phosphate (G-6-P) concentrations. Under similar steady-state plasma concentrations of glucose (approximately 11 mmol/l) and insulin (approximately 340 pmol/l), rates of muscle glycogen synthesis were reduced approximately 70% in the obese subjects (52 +/- 8 micromol/[l muscle-min]) as compared with the rates in the lean subjects (176 +/- 22 micromol/[l muscle-min]; P < 0.0001). Basal concentrations of intramuscular G-6-P were similar in the obese and lean subjects; but during the clamp, G-6-P failed to increase in the obese group (deltaG-6-P obese 0.044 +/- 0.011 vs. lean 0.117 +/- 0.011 mmol/l muscle; P < 0.001), reflecting decreased muscle glucose transport and/or phosphorylation activity. We conclude that insulin resistance in obesity can be mostly attributed to impairment of insulin-stimulated muscle glycogen synthesis due to a defect in glucose transport and/or phosphorylation activity.

Adult↗
PubMed1997

Mechanism of impaired insulin-stimulated muscle glucose metabolism in subjects with insulin-dependent diabetes mellitus.

To determine the mechanism of impaired insulin-stimulated muscle glycogen metabolism in patients with poorly controlled insulin-dependent diabetes mellitus (IDDM), we used 13C-NMR spectroscopy to monitor the peak intensity of the C1 resonance of the glucosyl units in muscle glycogen during a 6-h hyperglycemic-hyperinsulinemic clamp using [1-(13)C]glucose-enriched infusate followed by nonenriched glucose. Under similar steady state (t = 3-6 h) plasma glucose (approximately 9.0 mM) and insulin concentrations (approximately 400 pM), nonoxidative glucose metabolism was significantly less in the IDDM subjects compared with age-weight-matched control subjects (37+/-6 vs. 73+/-11 micromol/kg of body wt per minute, P < 0.05), which could be attributed to an approximately 45% reduction in the net rate of muscle glycogen synthesis in the IDDM subjects compared with the control subjects (108+/-16 vs. 195+/-6 micromol/liter of muscle per minute, P < 0.001). Muscle glycogen turnover in the IDDM subjects was significantly less than that of the controls (16+/-4 vs. 33+/-5%, P < 0.05), indicating that a marked reduction in flux through glycogen synthase was responsible for the reduced rate of net glycogen synthesis in the IDDM subjects. 31P-NMR spectroscopy was used to determine the intramuscular concentration of glucose-6-phosphate (G-6-P) under the same hyperglycemic-hyperinsulinemic conditions. Basal G-6-P concentration was similar between the two groups (approximately 0.10 mmol/kg of muscle) but the increment in G-6-P concentration in response to the glucose-insulin infusion was approximately 50% less in the IDDM subjects compared with the control subjects (0.07+/-0.02 vs. 0.13+/-0.02 mmol/kg of muscle, P < 0.05). When nonoxidative glucose metabolic rates in the control subjects were matched to the IDDM subjects, the increment in the G-6-P concentration (0.06+/-0.02 mmol/kg of muscle) was no different than that in the IDDM subjects. Together, these data indicate that defective glucose transport/phosphorylation is the major factor responsible for the lower rate of muscle glycogen synthesis in the poorly controlled insulin-dependent diabetic subjects.

Adult↗
PubMed1997

In vivo NMR investigation of intramuscular glucose metabolism in conscious rats.

In vivo 13C nuclear magnetic resonance (NMR) spectroscopy was used to determine quantitatively the flux of muscle glycolysis, glycogen synthesis, pyruvate dehydrogenase, and pyruvate carboxylation in the hindlimb of conscious rats. 13C NMR spectroscopy was used to observe [1-13C]glucose label precursor incorporation into intramuscular [1-13C]glycogen, [3-13C]lactate, and [3-13C]alanine during a hyperglycemic (approximately 11 mM)-hyperinsulinemic (10 mU.kg-1.min-1) clamp. The glycogen synthesis rate was calculated to be 224 +/- 23 nmol.g-1.min-1. The kinetic data obtained from the label turnover in the intramuscular C-3 lactate and C-3 alanine metabolite pools, as well as in plasma C-3 lactate and C-3 alanine, were combined with a steady-state rate analysis to determine the glycolytic flux (67.4 +/- 10.1 nmol.g-1.min-1). Steady-state isotopomer analysis of glutamate and pyruvate in skeletal muscle tissue extracts was used to determine the anaplerotic contribution of substrate via pyruvate carboxylation (Vpc). The pyruvate dehydrogenase flux (Vpdh) was calculated after a steady-state flux correction for Vpc. Calculated values of Vpc and Vpdh were 24.8 +/- 4.3 and 110.0 +/- 18.7 nmol.g-1.min-1, respectively. In addition, [2-13C]acetate was used in a separate study to determine that pyruvate carboxylation was the major pathway for anaplerosis in skeletal muscle under conditions of hyperglycemia-hyperinsulinemia.

Alanine↗
PubMed1997

Effects of insulin-like growth factor I on glucose metabolism in rats with liver cirrhosis.

To determine the effect of insulin-like growth factor I (IGF-I) on glucose metabolism in cirrhosis, a 2-h euglycemic clamp with IGF-I (0.65 nmol.kg-1.min-1) or insulin (12 pmol.kg-1.min-1) was performed in awake rats with carbon tetrachloride-induced liver cirrhosis. Rates of [3-3H]glucose-determined whole body glucose turnover were similar in the fasting state in cirrhotic and control rats (36.4 +/- 2.6 and 37.7 +/- 2.8 mumol.kg-1.min-1, respectively). In the control group, IGF-I and insulin had similar effects on turnover (81.6 +/- 27.0 and 76.1 +/- 9.9 mumol.kg-1.min-1), muscle glycogen synthesis (47.5 +/- 12.3 and 37.5 +/- 2.5 nmol.g muscle-1.min-1), and suppression of endogenous glucose production (EGP; -54 +/- 14 and -60 +/- 12%). Cirrhotic rats were markedly insulin resistant, reflected by a 43% reduction of turnover (43.8 +/- 9.4 mumol.g muscle-1.min-1; P = 0.03), a 73% reduction in muscle glycogen synthesis (10.2 +/- 3.4 nmol.g muscle-1.min-1; P < 0.0001), and a diminished suppression of EGP (-32 +/- 17% vs. control: -56 +/- 14%; P < 0.05). In contrast, during the IGF-I clamps, turnover increased threefold in the cirrhotic rats (P = 0.001), rates of muscle glycogen synthesis were 7.4 times higher than during the insulin stimulation (P < 0.0001), and EGP was suppressed by 80 +/- 12% (P < 0.05). In conclusion, insulin resistance in cirrhotic rats is mostly due to defects in insulin-stimulated muscle glycogen synthesis, and the ability of IGF-I to stimulate muscle glycogen synthesis as well as suppress EGP is maintained in cirrhotic rats. These findings suggest that alterations in both hepatic and peripheral glucose metabolism in patients with cirrhosis might be amenable to IGF-I therapy.

Animals↗
PubMed1996

Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects.

BACKGROUND: Insulin resistance in the offspring of parents with non-insulin-dependent diabetes mellitus (NIDDM) is the best predictor of development of the disease and probably plays an important part in its pathogenesis. We studied the mechanism and degree to which exercise training improves insulin sensitivity in these subjects. METHODS: Ten adult children of parents with NIDDM and eight normal subjects were studied before starting an aerobic exercise-training program, after one session of exercise, and after six weeks of exercise. Insulin sensitivity was measured by the hyperglycemic-hyperinsulinemic clamp technique combined with indirect calorimetry, and the rate of glycogen synthesis in muscle and the intramuscular glucose-6-phosphate concentration were measured by carbon-13 and phosphorus-31 nuclear magnetic resonance spectroscopy, respectively. RESULTS: During the base-line study, the mean (+/-SE) rate of muscle glycogen synthesis was 63 +/- 9 percent lower in the offspring of diabetic parents than in the normal subjects (P < 0.001). The mean value increased 69 +/- 10 percent (P = 0.04) and 62 +/- 11 percent (P = 0.04) after the first exercise session and 102 +/- 11 percent (P = 0.02) and 97 +/- 9 percent (P = 0.008) after six weeks of exercise training in the offspring and the normal subjects, respectively. The increment in glucose-6-phosphate during hyperglycemic-hyperinsulinemic clamping was lower in the offspring than in the normal subjects (0.039 +/- 0.013 vs. 0.089 +/- 0.009 mmol per liter, P = 0.005), reflecting reduced glucose transport-phosphorylation, but this increment was normal in the offspring after the first exercise session and after exercise training. Basal and stimulated insulin secretion was higher in the offspring than the normal subjects and was not altered by the exercise training program. CONCLUSIONS: Exercise increases insulin sensitivity in both normal subjects and the insulin-resistant offspring of diabetic parents because of a twofold increase in insulin-stimulated glycogen synthesis in muscle, due to an increase in insulin-stimulated glucose transport-phosphorylation.

Adult↗
PubMed1996

Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects.

All glucokinase gene mutations identified to date have been localized to exons that are common to the pancreatic and hepatic isoforms of the enzyme. While impaired insulin secretion has been observed in glucokinase-deficient subjects the consequences of this mutation on hepatic glucose metabolism remain unknown. To examine this question hepatic glycogen concentration was measured in seven glucokinase-deficient subjects with normal glycosylated hemoglobin and 12 control subjects using 13C nuclear magnetic spectroscopy during a day in which three isocaloric mixed meals were ingested. The relative fluxes of the direct and indirect pathways of hepatic glycogen synthesis were also assessed using [1-13C]glucose in combination with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. Average fasting hepatic glycogen content was similar in glucokinase-deficient and control subjects (279+/-20 vs 284+/-14 mM; mean+/-SEM), and increased in both groups after the meals with a continuous pattern throughout the day. However, the net increment in hepatic glycogen content after each meal was 30-60% lower in glucokinase-deficient than in the control subjects (breakfast, 46% lower, P < 0.02; lunch, 62% lower, P = 0.002; dinner; 30% lower, P = 0.04). The net increment over basal values 4 h after dinner was 105 +/-18 mM in glucokinase-deficient and 148+/-11 mM in control subjects (P = 0.04). In the 4 h after breakfast, flux through the gluconeogenic pathway relative to the direct pathway of hepatic glycogen synthesis was higher in glucokinase-deficient than in control subjects (50+/-2% vs 34+/-5%; P = 0.038). In conclusion glucokinase-deficient subjects have decreased net accumulation of hepatic glycogen and relatively augmented hepatic gluconeogenesis after meals. These results suggest that in addition to the altered beta cell function, abnormalities in liver glycogen metabolism play an important role in the pathogenesis of hyperglycemia in patients with glucokinase-deficient maturity onset diabetes of young.

Adult↗
PubMed1996

Mechanism of free fatty acid-induced insulin resistance in humans.

To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.

Adult↗
PubMed1996

The roles of insulin and glucagon in the regulation of hepatic glycogen synthesis and turnover in humans.

To determine the respective roles of insulin and glucagon for hepatic glycogen synthesis and turnover, hyperglycemic clamps were performed with somatostatin [0.1 micrograms/(kg.min)] in healthy young men under conditions of: (I) basal fasting) portal vein insulinemia-hypoglucagonemia, (II) basal portal vein insulinemia-basal glucagonemia, and (III) basal peripheral insulinemia-hypoglucagonemia. Synthetic rates, pathway (direct versus indirect) contributions, and percent turnover of hepatic glycogen were assessed by in vivo 13C nuclear magnetic resonance spectroscopy during [1-13C]glucose infusion followed by a natural abundance glucose chase in conjunction with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. In the presence of hyperglycemia (10.4 +/- 0.1 mM) and basal portal vein insulinemia (192 +/- 6 pM), suppression of glucagon secretion (plasma glucagon, I:31 +/- 4, II: 63 +/- 8 pg/ml) doubled the hepatic accumulation of glycogen (Vsyn) compared with conditions of basal glucagonemia [I: 0.40 +/- 0.06, II: 0.19 +/- 0.03 mumol/(liter.min): P < 0.0025]. Glycogen turnover was markedly reduced (I: 19 +/- 7%, II: 69 +/- 12%; P < 0.005), so that net rate of glycogen synthesis increased approximately fivefold (P < 0.001) by inhibition of glucagon secretion. The relative contribution of gluconeogenesis (indirect pathway) to glycogen synthesis was lower during hypoglucagonemia (42 +/- 6%) than during basal glucagonemia (54 +/- 5%; P < 0.005). Under conditions of basal peripheral insulinemia (54 +/- 2 pM) and hypoglucagonemia (III) there was negligible hepatic glycogen synthesis and turnover. In conclusion, small changes in portal vein concentrations of insulin and glucagon independently affect hepatic glycogen synthesis and turnover. Inhibition of glucagon secretion under conditions of hyperglycemia and basal concentrations of insulin results in: (a) twofold increase in rate of hepatic glycogen synthesis, (b) reduction of glycogen turnover by approximately 73%, and (c) augmented percent contribution of the direct pathway to glycogen synthesis compared with conditions of basal glucagonemia.

Adult↗
PubMed1996

Noninvasive assessment of hepatic triglyceride content in humans with 13C nuclear magnetic resonance spectroscopy.

Hepatic lipid content was assessed noninvasively in 15 patients with hepatic steatosis by 13C nuclear magnetic resonance (NMR) spectroscopy, and compared in a double-blind fashion with histological grading and morphometric quantitation of fat in liver biopsies taken within 2 weeks of the study. The lipid content in the liver biopsies was expressed as the volume fraction of total parenchyma occupied by fat. Hepatic triglyceride content was determined by comparing the 13C NMR signal intensity in vivo with the signal intensity obtained from a lipid phantom of known concentrations. There was an approximately 30-fold increase in the 13C NMR signals of the saturated carbons (methyl/methylene [CH2]n) region of hepatic triglycerides from patients with grade 4 steatosis compared with those with grade 0, yielding a good dynamic range for measuring hepatic triglyceride content. The correlation coefficient between the morphometric and 13C NMR techniques was 0.89 (P < .01). These studies demonstrate that 13C NMR spectroscopy can be used to noninvasively assess hepatic triglyceride content in humans. This method may be clinically useful for diagnosis and follow-up of patients with hepatic steatosis.

Adult↗
PubMed1996

Contribution of net hepatic glycogenolysis to glucose production during the early postprandial period.

Relative contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production during the first 12 h of a fast were studied in 13 healthy volunteers by noninvasively measuring hepatic glycogen content using 13C nuclear magnetic resonance spectroscopy. Rates of net hepatic glycogenolysis were calculated by multiplying the change in liver glycogen content with liver volume determined by magnetic resonance imaging. Rates of gluconeogenesis were calculated as the difference between rates of glucose production determined with an infusion of [6,6-2H]-glucose and net hepatic glycogenolysis. At 6 P.M. a liquid mixed meal (1,000 kcal; 60% as glucose) was given, to which [2-2H]glucose was added to trace glucose absorption. Hepatic glycogen content was measured between 11 P.M. and 1 A.M. and between 3 and 6 A.M. At 11 P.M. the concentration was 470 mM and it decreased linearly during the night. The mean liver volume was 1.47 +/- 0.06 liters. Net hepatic glycogenolysis (5.8 +/- 0.8 mumol.kg body wt-1.min-1) accounted for, on average, 45 +/- 6% and gluconeogenesis for 55 +/- 6% of the rate of whole body glucose production (12.6 +/- 0.6 mumol.kg body wt-1.min-1). In conclusion, this study shows that, even early in the phase of the postabsorptive period when liver glycogen stores are maximal, gluconeogenesis contributes approximately 50% to hepatic glucose production.

Adult↗
PubMed1995

Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver.

The relative roles of pyruvate kinase and malic enzyme in substrate cycling between pyruvate and oxaloacetate were examined in perfused livers of 24-hour-fasted normal and triiodothyronine (T3)-treated rats using an inhibitor of malic enzyme (hydroxymalonate). Livers were perfused for 60 minutes in a recirculating system with [3-13C]alanine (10 mmol/L, 99% 13C-enriched). The combined flux through pyruvate kinase plus malic enzyme relative to pyruvate carboxylase flux was assessed by the 13C-enrichment ratio of alanine C2 to glucose C5 in the perfusate, determined with 13C and 1H nuclear magnetic resonance (NMR) spectroscopy. In normal rat livers, the relative carbon flux through pyruvate kinase plus malic enzyme to pyruvate carboxylase was 0.18 +/- 0.04, and increased to 0.44 +/- 0.08 (P < .05) in the T3-treated group. After addition of hydroxymalonate, this relative carbon flux was unchanged in normal rat livers, but decreased to 0.15 +/- 0.04 (P < .01) in the T3-treated group, suggesting that the increased carbon flux in T3-treated livers was caused by increased flux through malic enzyme. Malic enzyme activity increased from 0.36 +/- 0.05 U/g liver in normal livers to 2.51 +/- 0.50 U/g liver (P < .05) in the T3-treated group, whereas there was no effect of T3 treatment on pyruvate kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1995

Impaired net hepatic glycogen synthesis in insulin-dependent diabetic subjects during mixed meal ingestion. A 13C nuclear magnetic resonance spectroscopy study.

Hepatic glycogen concentration was measured in six subjects with insulin-dependent diabetes mellitus (IDDM) and nine weight-matched control subjects using 13C nuclear magnetic resonance spectroscopy during a day in which three isocaloric mixed meals were ingested. The relative fluxes of the direct and indirect (3 carbon units-->-->glycogen) pathways of hepatic glycogen synthesis were also assessed using [1-13C]glucose in combination with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. Mean fasting hepatic glycogen content was similar in the two groups. After each meal, hepatic glycogen content increased, peaking 4-5 h after the meal in both groups. By 11:00 p.m. the IDDM subjects had synthesized only 30% of the glycogen that was synthesized by the control group [IDDM subjects, net increment = 44 +/- 20 (mean +/- SE) mM; control subjects, net increment = 144 +/- 14 mM; P < 0.05]. After breakfast the flux through the gluconeogenic pathway relative to the direct pathway of hepatic glycogen synthesis was 1.7-fold greater in the IDDM subjects (59 +/- 4%) than in the control subjects (35 +/- 4%, P < 0.0003). In conclusion, under mixed meal conditions, subjects with poorly controlled IDDM have a major defect in net hepatic glycogen synthesis and augmented hepatic gluconeogenesis. The former abnormality may result in an impaired glycemic response to counterregulatory hormones, whereas both abnormalities may contribute to postprandial hyperglycemia.

Adult↗
PubMed1994

A liver factor increasing glucose uptake in rat hindquarters.

The effect of the liver on glucose uptake in muscle was studied in the isolated rat hindquarter, perfused with and without an isolated rat liver included in a recirculating system. Glucose uptake in the hindquarter was 0.75 +/- 0.10 mumol.min-1 x 100 g bw-1 (mean and SEM), and increased to 1.30 +/- 0.12 during the period when the liver was included in the perfusion (N = 17; p = 0.0001). In experiments where tissue extracts were added to the perfusate during the second period, raw liver extracts increased the glucose uptake from 0.87 +/- 0.11 to 1.25 +/- 0.10 (N = 6; p = 0.003). Deproteinized liver and kidney extracts increased glucose uptake similarly. When the liver and hindquarter were perfused together during the first period, the glucose uptake in the hindquarter was 1.55 +/- 0.16 mumol.min-1 x 100 g bw-1 and decreased gradually during the period of isolated perfusion to 1.27 +/- 0.16 (N = 4; p = 0.15). In control experiments where tissue free extract fluid was added to the perfusate during the second period, or where the hindquarter was perfused either alone or with the liver during both periods, glucose uptake decreased slightly from 0.87 +/- 0.18 to 0.80 +/- 0.13 (N = 9; p = 0.2). In conclusion, a factor from the liver may increase the glucose uptake in muscle tissues. This factor is present in extracts from the liver and kidney, it is probably not a protein, but its nature is not known. It is speculated that glucose intolerance in patients with liver disease may be related to a lack of this factor.

Animals↗
PubMed1994

Substrate cycling between pyruvate and oxaloacetate in awake normal and 3,3'-5-triiodo-L-thyronine-treated rats.

Substrate cycling between pyruvate and oxaloacetate was assessed in awake 24-h fasted normal and triiodothyronine (T3)-treated rats. After a 20- or 60-min infusion of [3-13C]alanine (99% enriched, 12 mg/min) the 13C enrichments of liver glucose and alanine carbons were analyzed by 13C and 1H nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry. Substrate cycling from phosphoenolpyruvate to pyruvate [via pyruvate kinase (PK)] and from oxaloacetate to pyruvate [via malic enzyme (ME)] relative to the pyruvate carboxylase (PC) flux [i.e., (PK+ME)/PC] was assessed by the ratio of the 13C enrichment of C-2 alanine relative to that in C-5 glucose. In the normal rats (PK+ME)/PC was 0.26 +/- 0.07 (n = 7, t = 20 min) and 0.37 +/- 0.08 (n = 4, t = 60 min). In the T3-treated rats the (PK+ME)/PC increased four- to fivefold to 1.03 +/- 0.19 (n = 8, t = 20 min) and to 1.83 +/- 0.19 (n = 3, t = 60 min) (P < 0.05 vs. normal rats). The liver enzyme activity of PK did not change with T3 treatment (normal 14.22 +/- 5.25 U/g liver vs. T3 treated 13.40 +/- 1.10 U/g liver), whereas both the enzyme activity ratio of PK (normal 0.47 +/- 0.15 vs. T3 treated 0.77 +/- 0.03, P < 0.05) and the activity of ME (normal 0.89 +/- 0.30 U/g liver vs. T3 treated 4.25 +/- 0.60 U/g liver, P < 0.05) increased with T3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1993

Gluconeogenesis in hepatocytes determined with [2-13C]acetate and quantitative 13C NMR spectroscopy.

1. In the present study the major metabolic pathways of glucose metabolism were determined in isolated liver cells using [2-13C]acetate and 13C magnetic resonance spectroscopy. 2. The relative reaction rates of glucose synthesis to the TCA cycle were determined from the 13C distribution in glucose where the overall 13C enrichment of glucose was 6.41 +/- 1.94% (mean +/- SD; n = 6) and the mean 13C enrichment of C1, C2, C5, C6 to C3, C4 was 2.63 +/- 0.30. 3. Since the distribution of tracer in glucose is a function of the relative entry rates of pyruvate to acetyl-CoA into the oxaloacetate pool this was calculated to be 0.32 +/- 0.15 and the factor for carbon exchange (1/P) between the gluconeogenic pathway and the TCA cycle was calculated to be 1.03 +/- 0.20. 4. With this carbon exchange factor and the approximated 13C enrichment of acetyl-CoA the intramitochondrial 13C enrichment of phosphoenolpyruvate was calculated and the "true" rate of hepatic gluconeogenesis from phosphoenolpyruvate estimated. 5. Since acetate was metabolized solely in liver cells the 13C enrichment of acetyl-CoA could be approximated from that of 3-hydroxybutyrate. 6. The carbon 13 enrichment of 3-hydroxybutyrate and phosphoenolpyruvate was 5.89 +/- 0.90% and 5.96 +/- 1.67%, respectively. 7. The per cent gluconeogenesis from phosphoenolpyruvate calculated as the ratio of the 13C enrichment of glucose to that of 3-hydroxybutyrate times 1/P was 107 +/- 8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗