Differential effect of hyperglycemia and hyperinsulinemia on pathways of hepatic glycogen repletion

1991 ◽  
Vol 260 (5) ◽  
pp. E731-E735 ◽  
Author(s):  
G. I. Shulman ◽  
R. A. DeFronzo ◽  
L. Rossetti
Keyword(s):  
Portal Vein ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
Glycogen Repletion

To delineate the roles of hyperglycemia and insulin on the direct vs. indirect pathways of liver glycogen synthesis, we performed euglycemic (group I; n = 8), hyperglycemic (group II; n = 9), and euglycemic pharmacological hyperinsulinemic clamp studies (120 min) with an infusion of [1-13C]glucose in chronically catheterized conscious rats after a 24-h fast. Portal vein plasma glucose concentrations and portal vein plasma insulin concentrations, respectively, obtained at the end of the study in groups I-III were as follows: group I 110 +/- 4 mg/dl, 29 +/- 7 ng/ml; group II 219 +/- 7 mg/dl, 24 +/- 7 ng/ml; and group III 112 +/- 9 mg/dl, 174 +/- 25 ng/ml. Mean liver glycogen concentrations at the end of the three studies were 0.68 +/- 0.07, 1.22 +/- 0.08 (P less than 0.001 compared with groups I and III), and 0.60 +/- 0.17 g/100 g wet wt liver in groups I-III respectively, which yielded hepatic glycogen synthetic rates of 0.16 +/- 0.03, 0.41 +/- 0.04 (P less than 0.001 compared with groups I and III), and 0.13 +/- 0.08 mumol glucosyl U.g liver-1.min-1 in groups I-III, respectively. From the enrichments of 13C in the C-1 and C-6 positions of the glucosyl unit in glycogen compared with the enrichment in the C-1 position in portal vein glucose as determined by 13C- and 1H-NMR, the amount of glycogen synthesized by the direct pathway was calculated to be 18 +/- 2, 41 +/- 3 (P less than 0.0001 compared with groups I and III), and 17 +/- 3% in groups I-III, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of the route of glucose administration on hepatic glycogen repletion

1989 ◽  
Vol 257 (5) ◽  
pp. E681-E685 ◽  
Author(s):  
G. I. Shulman ◽  
L. Rossetti
Keyword(s):  
Portal Vein ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Intravenous Route ◽  
Hepatic Glycogen ◽  
Glucose Administration ◽  
Intraduodenal Infusion ◽  
Group Iii ◽  
Group I ◽  
Group Ii

To delineate the role of the route of glucose administration on liver glycogen synthesis, we administered [1-13C]glucose either by intravenous or intraduodenal infusion to chronically catheterized 24-h fasted rats and performed 1) intravenous-hyperglycemic clamp (group I, n = 9), portal vein plasma glucose and insulin concentrations were 216 +/- 6 mg/dl and 23.9 +/- 4.2 ng/ml; 2) intraduodenal-hyperglycemic infusion (group II, n = 8), portal vein glucose and insulin concentrations were 219 +/- 6 mg/dl and 17.5 +/- 2.7 ng/ml; and 3) intravenous-hyperglycemic-suprahyperinsulinemic clamp (group III, n = 5), portal vein glucose and insulin concentrations were 203 +/- 12 mg/dl and 44.6 +/- 5.0 ng/ml. The mean glucose infusion rates (mumol.kg-1.min-1) and glycogenic rates (mumol.g liver-1.min-1) were 201 +/- 8, 0.34 +/- 0.05; 129 +/- 3, 0.73 +/- 0.11; and 269 +/- 19, 0.38 +/- 0.08 in groups I-III, respectively. The percent of glycogen synthesized by the direct pathway was group I = 43 +/- 6%, group II = 44 +/- 6%, and group III = 46 +/- 7%. In conclusion, despite similar or lower portal vein insulin and glucose concentrations, the intraduodenal route of glucose administration (group II), compared with the intravenous route (groups I and III), markedly increased the total amount of liver glycogen synthesized without altering the percent of the direct vs. indirect pathways by which liver glycogen was repleted.

Plasma glucose concentration determines direct versus indirect liver glycogen synthesis

1986 ◽  
Vol 251 (5) ◽  
pp. E584-E590 ◽  
Author(s):  
C. H. Lang ◽  
G. J. Bagby ◽  
H. L. Blakesley ◽  
J. L. Johnson ◽  
J. J. Spitzer
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Infusion Rate ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Hepatic Glycogen ◽  
Glucose Load ◽  
Indirect Pathway

In the present study hepatic glycogenesis by the direct versus indirect pathway was determined as a function of the glucose infusion rate. Glycogen synthesis was examined in catheterized conscious rats that had been fasted 48 h before receiving a 3-h infusion (iv) of glucose. Glucose, containing tracer quantities of [U-14C]- and [6-3H]glucose, was infused at rates ranging from 0 to 230 mumol X min-1 X kg-1. Plasma concentrations of glucose, lactate, and insulin were positively correlated with the glucose infusion rate. Despite large changes in plasma glucose, lactate, and insulin concentrations, the rate of hepatic glycogen deposition (0.46 +/- 0.03 mumol X min-1 X g-1) did not vary significantly between glucose infusion rates of 20 and 230 mumol X min-1 X kg-1. However, the percent contribution of the direct pathway to glycogen repletion gradually increased from 13 +/- 2 to 74 +/- 4% in the lowest to the highest glucose infusion rates, with prevailing plasma glucose concentrations from 9.4 +/- 0.5 to 21.5 +/- 2.1 mM. Endogenous glucose production was depressed (by up to 40%), but not abolished by the glucose infusions. Only a small fraction (7-14%) of the infused glucose load was incorporated into liver glycogen via the direct pathway irrespective of the glucose infusion rate. Our data indicate that the relative contribution of the direct and indirect pathways of hepatic glycogen synthesis are dependent on the glucose load or plasma glucose concentration and emphasize the predominance of the indirect pathway of glycogenesis at plasma glucose concentrations normally observed after feeding.

Plasma glucose and insulin responses in growing rats fed a total parenteral nutrition diet either intravenously or intragastrically

1984 ◽  
Vol 62 (7) ◽  
pp. 775-780 ◽  
Author(s):  
Norman S. Track ◽  
Ernest Cutz ◽  
Barbara H. Witt
Keyword(s):  
Amino Acid ◽  
Parenteral Nutrition ◽  
Total Parenteral Nutrition ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Glucose Levels ◽  
Group I ◽  
Plasma Insulin Levels ◽  
Group Ii ◽  
Insulin Responses

The effect of administering either intravenously (group I) or intragastrically (group II) a glucose – amino acid total parenteral nutrition diet over a 12-day period upon plasma glucose and insulin responses was examined in adolescent rats. Infusion of the 25% glucose – 12.2% amino acid diet at a rate of 300 kCal∙kg body weight−1∙24 h−1 supported normal weight gain over the 12-day study period in both intravenously (group I) and intragastrically (group II) alimented rats. Mean plasma glucose levels rose dramatically in both groups by the end of day 1; group I had significantly higher mean plasma insulin levels. By day 3, the group I mean plasma glucose value decreased significantly while the group II mean glucose value remained virtually unchanged. Mean plasma insulin values more than doubled in both groups with the group I level still remaining significantly above the group II level. At days 6 and 12, group I mean plasma glucose levels were significantly below group II while both groups had similar plasma insulin levels. Data from this 12-day intravenous–intragastric alimentation study reveals quite different metabolic responses compared with acute (120–180 min) studies of the enteroinsular axis.

scholarly journals A COMPARATIVE STUDY OF EFFICACY AND SAFETY AMONG METFORMIN WITH SITAGLIPTIN, METFORMIN WITH VOGLIBOSE, AND METFORMIN WITH GLIMEPIRIDE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

2017 ◽  
Vol 10 (12) ◽  
pp. 313
Author(s):  
Kala P ◽  
Jamuna Rani R ◽  
Kumar Js
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Plasma Glucose ◽  
P Value ◽  
Efficacy And Safety ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Objective: Type 2 diabetes mellitus (DM) is a most common metabolic disorder. The present study aimed to compare the efficacy and safety among metformin with sitagliptin, metformin with voglibose, and metformin with glimepiride in patients with type 2 DM. Methods: This study was a prospective, randomized clinical trial study, conducted in patients attending the diabetology outpatient department of SRM Medical College Hospital and Research Center, Potheri, Kancheepuram, Tamil Nadu, from January 2013 to January 2014. The patients were randomized into three groups with 40 patients in each group. Fasting plasma glucose (FPG), 2 hrs postprandial plasma glucose (PPG), and hemoglobin A1c (HbA1c) level were assessed in all the patients before starting the treatment. In Group I, patients were prescribed metformin 500 mg with sitagliptin 50 mg, in Group II, patients were given metformin 500 mg with voglibose 0.2 mg, and in Group III, patients were put on metformin 500 mg with glimepiride 1 mg in the fixed combination. The outcome of the therapy was based on the level of improvement in the blood parameters. Results: There was a significant reduction of FPG level seen in all three groups (p value - Group I <0.0001, Group II < 0.005, and Group III <0.0001). Group I and III showed significant reduction of PPG with p value <0.0001. There was a significant reduction of HbA1c seen in all the three groups (p<0.0001). Conclusion: From the results of this study, it could be concluded that all the three groups were comparable in their efficacy.

Quantitative comparison of pathways of hepatic glycogen repletion in fed and fasted humans.

1990 ◽  
Vol 259 (3) ◽  
pp. E335 ◽  
Author(s):  
G I Shulman ◽  
G Cline ◽  
W C Schumann ◽  
V Chandramouli ◽  
K Kumaran ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Specific Activity ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Moderate Amount ◽  
Dietary Regimen ◽  
Direct Pathway ◽  
Glycogen Repletion ◽  
The Individual ◽  
Glycogen Formation

The effect of fasting vs. refeeding on hepatic glycogen repletion by the direct pathway, i.e., glucose----glucose 6-phosphate (G-6-P)----glycogen, was determined. Acetaminophen was administered during an infusion of glucose labeled with [1-13C]- and [6-14C]glucose into four healthy volunteers after an overnight fast and into the same subjects 4 h after breakfast. 13C enrichments in C-1 and C-6 of glucose formed from urinary acetaminophen glucuronide compared with enrichments in C-1 and C-6 of plasma glucose provided an estimate of glycogen formation by the direct pathway. The specific activity of glucose from the glucuronide compared with the specific activity of the plasma glucose, along with the percentages of 14C in C-1 and C-6 of the glucose from the glucuronide, also provided an estimate of the amount of glycogen formed by the direct pathway. The estimates were similar. Those from [6-14C]glucose would have been higher than from [1-13C]glucose if the pentose cycle contribution to overall glucose utilization had been significant. After an overnight fast, during the last hour of infusion, 49 +/- 3% of the glycogen formed was formed via the direct pathway. After breakfast, at similar plasma glucose and insulin concentrations, the percentage increased to 69 +/- 7% (P less than 0.02). Thus the contributions of the pathways to hepatic glycogen formation depend on the dietary state of the individual. For a dietary regimen in which individuals consume multiple meals per day containing at least a moderate amount of carbohydrates most glycogen synthesis occurs by the direct pathway.

Abstract 84: The Effect of Hyperglycemia on Stroke Outcome Depends on Baseline Glycosylated Hemoglobin Levels

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Kwang-Yeol Park ◽  
Johanna Helenius ◽  
Ross Avery ◽  
Gyeong-Moon Kim ◽  
Ferdinando S Buonanno ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Plasma Glucose ◽  
Hba1c Level ◽  
Infarct Volume ◽  
Glycosylated Hemoglobin ◽  
Unfavorable Outcome ◽  
Baseline Hba1c ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Background and hypothesis: Patients with diabetes mellitus (DM) are less likely to develop adverse outcomes than are those without DM in response to acute elevations in plasma glucose after stroke. We hypothesized that baseline glycosylated hemoglobin (HbA1c) level, which provides an estimate of long-term plasma glucose concentration, inversely correlated with clinical and tissue outcome in acute ischemic stroke patients presenting with hyperglycemia. Methods: Within the context of an ongoing prospective study (Heart-Brain Interactions Study), we measured plasma glucose and HbA1c levels in 1080 patients with acute ischemic stroke within 72 hours of symptom onset. We classified patients into 3 HbA1c strata based on the American Diabetes Association criteria: group-I (HbA1c <5.7%, n=439), group-II (HbA1c: 5.7 to 6.4%, n=290), group-III (known DM or HbA1c >6.4, n=351). We examined the relationship between admission blood glucose level, acute infarct volume on DWI, and unfavorable outcome (mRS≥3) at 3 months in each HbA1c stratum. Results: The probability of unfavorable outcome decreased by increasing baseline HbA1c level; the OR (95% CI) for unfavorable outcome for every 10 mg/dl increase in glucose level was 1.42 (1.25-1.62) in group-I, 1.19 (1.07-1.33) in group-II, and 1.02 (0.99-1.05) in group-III. When hyperglycemia was defined as ≥144 mg/dl, OR (95% CI) for unfavorable outcome was 6.53 (2.65-16.14) in group-I, 1.56 (0.77-3.15) in group-II, and 1.35 (0.78-2.33) in group-III. Adjusting for age and sex did not change the results. For every 10 ml elevation in plasma glucose, the mean infarct volume increased by 7.45 ml (5.04-9.85) in group-I, 4.96 ml (2.82-7.09) in group-II, and 0.73 ml (-0.24-1.70) in group-III. Conclusions: Chronic hyperglycemia appears to protect from deleterious effects of acute elevations in blood glucose after ischemic stroke. Further research is warranted examining whether baseline HbA1c concentration predicts benefit from interventions for glycemic control in acute stroke.

scholarly journals Effects of lactate on pathways of glycogen formation in the perfused rat liver

1991 ◽  
Vol 280 (2) ◽  
pp. 415-419 ◽  
Author(s):  
Z Zhang ◽  
J Radziuk
Keyword(s):  
Direct Synthesis ◽  
Liver Perfusion ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Group I ◽  
Lactate Uptake ◽  
Group Ii ◽  
Lactate Infusion ◽  
Glycogen Formation

In order to investigate the roles of lactate as substrate and regulator of hepatic glycogen synthesis, two groups of rat livers were perfused with oxygenated blood for 2 h. The initial perfusate glucose and lactate concentrations of Group I and II were 245 +/- 6.8 and 254 +/- 12.9 mg/dl and 49 +/- 2.6 and 54 +/- 2.2 mg/dl respectively. Labelled glucose was added to the perfusate to assess direct glycogen formation. Either additional glucose (Group I) or lactate (Group II) was added (1 mg/min) to a recirculating liver-perfusion system. Initial lactate uptake and glucose formation was identical in the two groups of studies. For Group I, both glucose and lactate uptake by the liver fell to nearly zero, in spite of increasing glucose concentrations. However, with lactate infusion (Group II), its uptake by the liver was maintained at 0.89 +/- 0.14 mg/min after 120 min. In total, 6.2 +/- 0.7 mg (Group I) or 20.2 +/- 3.9 mg (Group II) of glycogen was formed, 4.0 +/- 0.7 mg or 9.2 +/- 2.0 mg by direct synthesis from glucose and 2.2 +/- 0.3 mg or 11.0 +/- 2.1 mg by gluconeogenic formation, in Groups I and II respectively. With the provision of additional lactate, its uptake by the perfused liver tripled, as did glycogen synthesis. Glucose production doubled when lactate was added instead of glucose. Gluconeogenic formation of glycogen increased by 400%. Surprisingly, direct synthesis from glucose also rose by 130%. These data indicate that continued lactate uptake by the liver with gluconeogenic glycogen formation determines the amount of glycogen formed not only by this route, but also by direct synthesis from glucose.

Carbohydrate metabolism in fructose-fed and food-restricted running rats

1986 ◽  
Vol 61 (4) ◽  
pp. 1457-1466 ◽  
Author(s):  
B. Sonne ◽  
H. Galbo
Keyword(s):  
Carbohydrate Metabolism ◽  
Plasma Glucose ◽  
Direct Synthesis ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Treadmill Running ◽  
Hepatic Glycogen ◽  
Work Intensity ◽  
Glycogen Breakdown

In chronically catheterized rats hepatic glycogen was increased by fructose (approximately 10 g/kg) gavage (FF rats) or lowered by overnight food restriction (FR rats). [3-3H]- and [U-14C]glucose were infused before, during, and after treadmill running. During exercise the increase in glucose production (Ra) was always directly related to work intensity and faster than the increase in glucose disappearance, resulting in increased plasma glucose levels. At identical work-loads the increase in Ra and plasma glucose as well as liver glycogen breakdown were higher in FF and control (C) rats than in FR rats. Breakdown of muscle glycogen was less in FF than in C rats. Incorporation of [14C]glucose in glycogen at rest and mobilization of label during exercise partly explained that 14C estimates of carbohydrate metabolism disagreed with chemical measurements. In some muscles glycogen depletion was not accompanied by loss of 14C and 3H, indicating futile cycling of glucose. In FR rats a postexercise increase in liver glycogen was seen with 14C/3H similar to that of plasma glucose, indicating direct synthesis from glucose. In conclusion, in exercising rats the increase in glucose production is subjected to feedforward regulation and depends on the liver glycogen concentration. Endogenous glucose may be incorporated in glycogen in working muscle and may be used directly for liver glycogen synthesis rather than after conversion to trioses. Fructose ingestion may diminish muscular glycogen breakdown. The [14C]glucose infusion technique for determination of muscular glycogenolysis is of doubtful value in rats.

Ultrastructural Lesions Produced by Alcohol and Sucrose in the Heart and Liver of C57BL Mice

1970 ◽  
Vol 28 ◽  
pp. 208-209
Author(s):  
K.K. SEKHRI ◽  
C.S. ALEXANDER ◽  
H.T. NAGASAWA
Keyword(s):  
Osmium Tetroxide ◽  
Male Mice ◽  
Alcohol Group ◽  
Group Iii ◽  
Group I ◽  
C57bl Mice ◽  
Group Ii

C57BL male mice (Jackson Lab., Bar Harbor, Maine) weighing about 18 gms were randomly divided into three groups: group I was fed sweetened liquid alcohol diet (modified Schenkl) in which 36% of the calories were derived from alcohol; group II was maintained on a similar diet but alcohol was isocalorically substituted by sucrose; group III was fed regular mouse chow ad lib for five months. Liver and heart tissues were fixed in 2.5% cacodylate buffered glutaraldehyde, post-fixed in 2% osmium tetroxide and embedded in Epon-araldite.

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