Increased basal glucose production and utilization in children with recent obesity versus adults with long-term obesity

Diabetes ◽  
1989 ◽  
Vol 38 (4) ◽  
pp. 477-483 ◽  
Author(s):  
P. F. Bougneres ◽  
E. Artavia-Loria ◽  
S. Henry ◽  
A. Basdevant ◽  
L. Castano
Keyword(s):  
Glucose Production

Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals

2007 ◽  
Vol 293 (6) ◽  
pp. R2376-R2381 ◽  
Author(s):  
Dorian S. Houser ◽  
Cory D. Champagne ◽  
Daniel E. Crocker
Keyword(s):  
Adult Female ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
High Rate ◽  
Constant Infusion ◽  
Substantial Contribution ◽  
Fasting Period ◽  
Elephant Seals ◽  
Glucoregulatory Hormones

Adult female elephant seals ( Mirounga angustirostris) combine long-term fasting with lactation and molting. Glycerol gluconeogenesis has been hypothesized as potentially meeting all of the glucose requirements of the seals during these fasts. To test this hypothesis, a primed constant infusion of [2-14C]glycerol was administered to 10 ten adult female elephant seals at 5 and 21–22 days postpartum and to 10 additional adult females immediately after the molt. Glycerol kinetics, rates of lipolysis, and the contribution of glycerol to glucose production were determined for each period. Plasma metabolite levels as well as insulin, glucagon, and cortisol were also measured. Glycerol rate of appearance was not significantly correlated with mass ( P = 0.14, r2 = 0.33) but was significantly related to the percentage of glucose derived from glycerol ( P < 0.01, r2 = 0.81) during late lactation. The contribution of glycerol to glucose production was <3% during each fasting period, suggesting a lower contribution to gluconeogenesis than is observed in other long-term fasting mammals. Because of a high rate of endogenous glucose production in fasting elephant seals, it is likely that glycerol gluconeogenesis still makes a substantial contribution to the substrate needs of glucose-dependent tissues. The lack of a relationship between glucoregulatory hormones and glycerol kinetics, glycerol gluconeogenesis, and metabolites supports the proposition that fasting elephant seals do not conform to the traditional insulin-glucagon model of substrate metabolism.

Increased epinephrine response and inaccurate glucoregulation in exercising athletes

1986 ◽  
Vol 61 (5) ◽  
pp. 1693-1700 ◽  
Author(s):  
M. Kjaer ◽  
P. A. Farrell ◽  
N. J. Christensen ◽  
H. Galbo
Keyword(s):  
Adrenal Medulla ◽  
Maximal Exercise ◽  
Nervous Activity ◽  
Glucose Production ◽  
Sympathetic Nervous Activity ◽  
Glucose Levels ◽  
Renal Threshold ◽  
Secretory Capacity ◽  
Stimulation Of

Epinephrine responses to insulin-induced hypoglycemia have indicated that athletes have a higher adrenal medullary secretory capacity than untrained subjects. This view was tested by an exercise protocol aiming at identical stimulation of the adrenal medulla in the two groups. Eight athletes (T) and eight controls (C) ran 7 min at 60% maximal O2 consumption (VO2max), 3 min at 100% VO2max, and 2 min at 110% VO2max. Plasma epinephrine both at rest and at identical relative work loads [110% VO2max: 8.73 +/- 1.51 (T) vs. 3.60 +/- 1.09 mmol X l-1 (C)] was higher [P less than 0.05) in T than in C. Norepinephrine, as well as heart rate, increased identically in the two groups, indicating identical sympathetic nervous activity. Lactate and glycerol were higher in T than in C after running. Glucose production peaked immediately after exercise and was higher in T than in C. Glucose disappearance increased less than glucose production and was identical in T and C. Accordingly plasma glucose increased, more in T than in C (P less than 0.01). In T glucose levels approached the renal threshold greater than 20 min postexercise. Glucose clearance increased less in T than in C during exercise and decreased postexercise to or below (T, P less than 0.05) basal levels, despite increased insulin levels. Long-term endurance training increases responsiveness of the adrenal medulla to exercise, indicating increased secretory capacity. During maximal exercise this may contribute to higher glucose production, lower clearance, more inaccurate glucoregulation, and higher lypolysis in T compared with C.

scholarly journals Mass spectrometry-based microassay of 2H and 13C plasma glucose labeling to quantify liver metabolic fluxes in vivo

2015 ◽  
Vol 309 (2) ◽  
pp. E191-E203 ◽  
Author(s):  
Clinton M. Hasenour ◽  
Martha L. Wall ◽  
D. Emerson Ridley ◽  
Curtis C. Hughey ◽  
Freyja D. James ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Glucose ◽  
Ad Hoc ◽  
Citrate Synthase ◽  
Physiological Stress ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Hepatic Glucose

Mouse models designed to examine hepatic metabolism are critical to diabetes and obesity research. Thus, a microscale method to quantitatively assess hepatic glucose and intermediary metabolism in conscious, unrestrained mice was developed. [13C3]propionate, [2H2]water, and [6,6-2H2]glucose isotopes were delivered intravenously in short- (9 h) and long-term-fasted (19 h) C57BL/6J mice. GC-MS and mass isotopomer distribution (MID) analysis were performed on three 40-μl arterial plasma glucose samples obtained during the euglycemic isotopic steady state. Model-based regression of hepatic glucose and citric acid cycle (CAC)-related fluxes was performed using a comprehensive isotopomer model to track carbon and hydrogen atom transitions through the network and thereby simulate the MIDs of measured fragment ions. Glucose-6-phosphate production from glycogen diminished, and endogenous glucose production was exclusively gluconeogenic with prolonged fasting. Gluconeogenic flux from phospho enolpyruvate (PEP) remained stable, whereas that from glycerol modestly increased from short- to long-term fasting. CAC flux [i.e., citrate synthase ( V CS)] was reduced with long-term fasting. Interestingly, anaplerosis and cataplerosis increased with fast duration; accordingly, pyruvate carboxylation and the conversion of oxaloacetate to PEP were severalfold higher than V CS in long-term fasted mice. This method utilizes state-of-the-art in vivo methodology and comprehensive isotopomer modeling to quantify hepatic glucose and intermediary fluxes during physiological stress in mice. The small plasma requirements permit serial sampling without stress and the affirmation of steady-state glucose kinetics. Furthermore, the approach can accommodate a broad range of modeling assumptions, isotope tracers, and measurement inputs without the need to introduce ad hoc mathematical approximations.

Increased Basal Glucose Production and Utilization in Children With Recent Obesity Versus Adults With Long-Term Obesity

Diabetes ◽  
1989 ◽  
Vol 38 (4) ◽  
pp. 477-483 ◽  
Author(s):  
P.-F. Bougneres ◽  
P. Artavia-Loria ◽  
S. Henry ◽  
A. Basdevant ◽  
L. Castano
Keyword(s):  
Glucose Production

scholarly journals Effect of macronutrients, age, and obesity on 6- and 24-h postprandial glucose metabolism in cats

2011 ◽  
Vol 301 (6) ◽  
pp. R1798-R1807 ◽  
Author(s):  
Margarethe Hoenig ◽  
Erin T. Jordan ◽  
John Glushka ◽  
Saskia Kley ◽  
Avinash Patil ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Pathways ◽  
Glucose Production ◽  
Postprandial Glucose ◽  
Endogenous Glucose Production ◽  
High Carbohydrate ◽  
Postprandial State ◽  
Peripheral Insulin Resistance ◽  
Important Pathway

Obesity and age are risk factors for feline diabetes. This study aimed to test the hypothesis that age, long-term obesity, and dietary composition would lead to peripheral and hepatorenal insulin resistance, indicated by higher endogenous glucose production (EGP) in the fasted and postprandial state, higher blood glucose and insulin, and higher leptin, free thyroxine, and lower adiponectin concentrations. Using triple tracer—2H2O, [U-13C3] propionate, and [3,4-13C2] glucose infusion, and indirect calorimetry—we investigated carbohydrate and fat metabolic pathways in overnight-fasted neutered cats (13 young lean, 12 old lean, and 12 old obese), each fed three different diets (high protein with and without polyunsaturated fatty acids, and high carbohydrate) in a crossover design. EGP was lowest in fasted and postprandial obese cats despite peripheral insulin resistance, indicated by hyperinsulinemia. Gluconeogenesis was the most important pathway for EGP in all groups, but glycogen contributed significantly. Insulin and leptin concentrations were higher in old than in young lean cats; adiponectin was lowest in obese cats but surprisingly highest in lean old cats. Diet had little effect on metabolic parameters. We conclude that hepatorenal insulin resistance does not develop in the fasted or postprandial state, even in long-term obese cats, allowing the maintenance of euglycemia through lowering EGP. Glycogen plays a major role in EGP, especially in lean fasted cats, and in the postprandial state. Aging may predispose to insulin resistance, which is a risk factor for diabetes in cats. Mechanisms underlying the high adiponectin of healthy old lean cats need to be further explored.

scholarly journals Long-Term Improvement in Glucose Control and Counterregulation by Islet Transplantation for Type 1 Diabetes

2016 ◽  
Vol 101 (11) ◽  
pp. 4421-4430 ◽  
Author(s):  
Michael R. Rickels ◽  
Amy J. Peleckis ◽  
Eileen Markmann ◽  
Cornelia Dalton-Bakes ◽  
Stephanie M. Kong ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
University Of Pennsylvania ◽  
Symptom Recognition ◽  
Endogenous Glucose ◽  
The University

Context: Islet transplantation has been shown to improve glucose counterregulation and hypoglycemia symptom recognition in patients with type 1 diabetes (T1D) complicated by severe hypoglycemia episodes and symptom unawareness, but long-term data are lacking. Objective: To assess the long-term durability of glucose counterregulation and hypoglycemia symptom responses 18 months after intrahepatic islet transplantation and associated measures of glycemic control during a 24-month follow-up period. Design, Setting, and Participants: Ten patients with T1D disease duration of approximately 27 years were studied longitudinally before and 6 and 18 months after transplant in the Clinical & Translational Research Center of the University of Pennsylvania and were compared to 10 nondiabetic control subjects. Intervention: All 10 patients underwent intrahepatic islet transplantation according to the CIT07 protocol at the Hospital of the University of Pennsylvania. Main Outcome Measures: Counterregulatory hormone, endogenous glucose production, and autonomic symptom responses derived from stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-2H2-glucose. Results: Near-normal glycemia (HbA1c ≤ 6.5%; time 70–180 mg/dL ≥ 95%) was maintained for 24 months in all patients, with one returning to low-dose insulin therapy. In response to insulin-induced hypoglycemia, glucagon secretion was incompletely restored at 6 and 18 months, epinephrine was improved at 6 months and normalized at 18 months, and endogenous glucose production and symptoms, absent before, were normalized at 6 and 18 months after transplant. Conclusions: In patients with T1D experiencing problematic hypoglycemia, intrahepatic islet transplantation can lead to long-term improvement of glucose counterregulation and hypoglycemia symptom recognition, physiological effects that likely contribute to glycemic stability after transplant.

Effects of training duration on substrate turnover and oxidation during exercise

1996 ◽  
Vol 81 (5) ◽  
pp. 2182-2191 ◽  
Author(s):  
S. M. Phillips ◽  
H. J. Green ◽  
M. A. Tarnopolsky ◽  
G. J. F. Heigenhauser ◽  
R. E. Hill ◽  
...  
Keyword(s):  
Glucose Production ◽  
Fat Oxidation ◽  
Progressive Increase ◽  
Mitochondrial Enzyme ◽  
Isotope Tracers ◽  
Fat Utilization ◽  
Plasma Ffa ◽  
Intramuscular Triglyceride ◽  
Total Fat

Phillips, S. M., H. J. Green, M. A. Tarnopolsky, G. J. F. Heigenhauser, R. E. Hill, and S. M. Grant. Effects of training duration on substrate turnover and oxidation during exercise. J. Appl. Physiol. 81(5): 2182–2191, 1996.—Adaptations in fat and carbohydrate metabolism after a prolonged endurance training program were examined using stable isotope tracers of glucose ([6,6-2H2]glucose), glycerol ([2H5]glycerol), and palmitate ([2H2]palmitate). Active, but untrained, males exercised on a cycle for 2 h/day [60% pretraining peak O2consumption (V˙o 2 peak) = 44.3 ± 2.4 ml ⋅ kg−1 ⋅ min−1] for a total of 31 days. Three cycle tests (90 min at 60% pretrainingV˙o 2 peak) were administered before training (PRE) and after 5 (5D) and 31 (31D) days of training. Exercise increased the rate of glucose production (Ra) and utilization (Rd) as well as the rate of lipolysis (glycerol Ra) and free fatty acid turnover (FFA Ra/Rd). At 5D, training induced a 10% ( P < 0.05) increase in total fat oxidation because of an increase in intramuscular triglyceride oxidation (+63%, P < 0.05) and a decreased glycogen oxidation (−16%, P < 0.05). At 31D, total fat oxidation during exercise increased a further 58% ( P < 0.01). The pattern of fat utilization during exercise at 31D showed a reduced reliance on plasma FFA oxidation (FFA Rd) and a greater dependence on oxidation of intramuscular triglyceride, which increased more than twofold ( P < 0.001). In addition, glucose Raand Rd were reduced at all time points during exercise at 31D compared with PRE and 5D. We conclude that long-term training induces a progressive increase in fat utilization mediated by a greater oxidation of fats from intramuscular sources and a reduction in glucose oxidation. Initial changes are present as early as 5D and occur before increases in muscle maximal mitochondrial enzyme activity [S. M. Phillips, H. J. Green, M. A. Tarnopolsky, G. J. F. Heigenhauser, and S. M. Grant. Am. J. Physiol. 270 ( Endocrinol. Metab. 33): E265–E272, 1996].

scholarly journals Hepatic Gluconeogenic Response to Single and Long-Term SGLT2 Inhibition in Lean/Obese Male Hepatic G6pc-Reporter Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (12) ◽  
pp. 2811-2824 ◽  
Author(s):  
Yuka Inaba ◽  
Emi Hashiuchi ◽  
Hitoshi Watanabe ◽  
Kumi Kimura ◽  
Makoto Sato ◽  
...  
Keyword(s):  
Single Dose ◽  
Blood Glucose ◽  
Plasma Insulin ◽  
Glucose Production ◽  
Obese Mice ◽  
Specific Expression ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Hepatic Insulin Signaling

Abstract Sodium-glucose cotransporter 2 inhibitor (SGLT2i) consistently reduces blood glucose levels in type 2 diabetes mellitus but increases hepatic gluconeogenic gene expression and glucose production, offsetting its glucose-lowering effect. This study aimed to elucidate the effect of SGLT2i on hepatic gluconeogenic response and its mechanism in both insulin-sensitive and insulin-resistant states. A hepatic mouse model was generated to show liver-specific expression of Gaussia luciferase (GLuc) driven by the gluconeogenic enzyme gene G6pc promoter. Hepatic gluconeogenic response was evaluated by measuring plasma GLuc activity. SGLT2i was given to lean and obese mice in single gavage administration or 4-week dietary administration with controlled feeding every 3 hours. In lean mice, single-dose SGLT2i increased plasma GLuc activity from 2 hours after administration, decreasing blood glucose and plasma insulin from 1 to 2 hours after administration. In obese mice, which had higher plasma GLuc activity than lean ones, SGLT2i did not further increase GLuc activity despite decreased blood glucose and plasma insulin. Hepatic Akt and GSK3β phosphorylation was attenuated by single-dose SGLT2i in lean mice in accordance with the plasma insulin decrease, but not in obese mice. Long-term SGLT2i administration, which increased plasma GLuc activity in lean mice, decreased it in obese mice from 3 weeks after initiation, with increased hepatic Akt and GSK3β phosphorylation. In conclusion, single SGLT2i administration increases hepatic gluconeogenic response in lean insulin-sensitive mice, but not in obese insulin-resistant mice. Long-term SGLT2i administration relieves obesity-induced upregulation of the hepatic gluconeogenic response by restoring impeded hepatic insulin signaling in obese insulin-resistant mice.

scholarly journals Dietary Fructose and the Metabolic Syndrome

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1987 ◽  
Author(s):  
Taskinen ◽  
Packard ◽  
Borén
Keyword(s):  
Metabolic Syndrome ◽  
Large Body ◽  
Glucose Production ◽  
Sweetened Beverages ◽  
Baked Goods ◽  
The Metabolic Syndrome ◽  
Dietary Fructose ◽  
Intrahepatic Lipid

Abstract: Consumption of fructose, the sweetest of all naturally occurring carbohydrates, has increased dramatically in the last 40 years and is today commonly used commercially in soft drinks, juice, and baked goods. These products comprise a large proportion of the modern diet, in particular in children, adolescents, and young adults. A large body of evidence associate consumption of fructose and other sugar-sweetened beverages with insulin resistance, intrahepatic lipid accumulation, and hypertriglyceridemia. In the long term, these risk factors may contribute to the development of type 2 diabetes and cardiovascular diseases. Fructose is absorbed in the small intestine and metabolized in the liver where it stimulates fructolysis, glycolysis, lipogenesis, and glucose production. This may result in hypertriglyceridemia and fatty liver. Therefore, understanding the mechanisms underlying intestinal and hepatic fructose metabolism is important. Here we review recent evidence linking excessive fructose consumption to health risk markers and development of components of the Metabolic Syndrome.

The Second Generation Sulfonylureas: Glipizide and Glyburide

1985 ◽  
Vol 11 (3) ◽  
pp. 29-36 ◽  
Author(s):  
Danial E. Baker ◽  
R. Keith Campbell
Keyword(s):  
Hepatic Glucose Production ◽  
Elevated Serum ◽  
Glucose Production ◽  
Serum Glucose ◽  
Glucose Levels ◽  
Diet And Exercise ◽  
Hepatic Glucose ◽  
Insulin Activity ◽  
Extrapancreatic Effects

Glyburide and glipizide are approved by the FDA for treatment of symptomatic and asymp tomatic NIDDM patients in whom hyperglycemia cannot be satisfactorily controlled by diet and exercise. Pharmacology studies suggest that glyburide and glipizide sensitize the beta cells of the pancreas to release insulin only in the presence of elevated serum glucose levels. Long-term efficacy appears to depend on extrapancreatic effects, suppressing hepatic glucose production, and improved postreceptor insulin activity.

Sign in / Sign up

Export Citation Format

Share Document