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.

Response to glucose infusion in humans: role of changes in insulin concentration

1986 ◽  
Vol 250 (3) ◽  
pp. E306-E311 ◽  
Author(s):  
R. R. Wolfe ◽  
J. H. Shaw ◽  
F. Jahoor ◽  
D. N. Herndon ◽  
M. H. Wolfe
Keyword(s):  
Insulin Response ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Hormonal Control ◽  
Glucose Infusion ◽  
High Rate ◽  
Constant Infusion ◽  
Urea Kinetics ◽  
Metabolic Interactions ◽  
Endogenous Glucose

We have used the primed-constant infusion of stable isotopes of glucose ([6,6-d2]glucose), alanine([3-13C] alanine), and urea ([15N2]urea) to investigate their kinetic interrelationships in normal volunteers in the postabsorptive state and during the infusion of unlabeled glucose at two rates. Each glucose infusion was tested with and without the simultaneous infusion of somatostatin (S), insulin (I), and glucagon (G) to clamp those hormonal levels. When glucose was infused at 1 mg X kg-1 X min-1, endogenous glucose production was suppressed almost exactly 1 mg X kg-1 X min-1, regardless of whether S plus I plus G were infused. The 4 mg X kg-1 X min-1 glucose infusion suppressed endogenous glucose production, both with and without hormonal control. The plasma concentration of glucose also increased to the same extent during the 4 mg X kg-1 X min-1 infusion in both protocols, which indicated that the spontaneous insulin response to the glucose infusion (an increase from 11 +/- 2 to 24 +/- 3 microU/ml) did not stimulate the peripheral clearance of glucose. The high rate of glucose infusion, both with or without hormonal control, stimulated alanine flux and inhibited urea production. These results indicate that glucose, per se, is an important direct controller of normal metabolic interactions of endogenous alanine, glucose, and urea kinetics.

Gluconeogenesis is associated with high rates of tricarboxylic acid and pyruvate cycling in fasting northern elephant seals

2012 ◽  
Vol 303 (3) ◽  
pp. R340-R352 ◽  
Author(s):  
Cory D. Champagne ◽  
Dorian S. Houser ◽  
Melinda A. Fowler ◽  
Daniel P. Costa ◽  
Daniel E. Crocker
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Endogenous Glucose Production ◽  
Large Contribution ◽  
Protein Loss ◽  
Elephant Seals ◽  
Pyruvate Cycling ◽  
Northern Elephant Seals

Animals that endure prolonged periods of food deprivation preserve vital organ function by sparing protein from catabolism. Much of this protein sparing is achieved by reducing metabolic rate and suppressing gluconeogenesis while fasting. Northern elephant seals ( Mirounga angustirostris) endure prolonged fasts of up to 3 mo at multiple life stages. During these fasts, elephant seals maintain high levels of activity and energy expenditure associated with breeding, reproduction, lactation, and development while maintaining rates of glucose production typical of a postabsorptive mammal. Therefore, we investigated how fasting elephant seals meet the requirements of glucose-dependent tissues while suppressing protein catabolism by measuring the contribution of glycogenolysis, glycerol, and phosphoenolpyruvate (PEP) to endogenous glucose production (EGP) during their natural 2-mo postweaning fast. Additionally, pathway flux rates associated with the tricarboxylic acid (TCA) cycle were measured specifically, flux through phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate cycling. The rate of glucose production decreased during the fast (F1,13= 5.7, P = 0.04) but remained similar to that of postabsorptive mammals. The fractional contributions of glycogen, glycerol, and PEP did not change with fasting; PEP was the primary gluconeogenic precursor and accounted for ∼95% of EGP. This large contribution of PEP to glucose production occurred without substantial protein loss. Fluxes through the TCA cycle, PEPCK, and pyruvate cycling were higher than reported in other species and were the most energetically costly component of hepatic carbohydrate metabolism. The active pyruvate recycling fluxes detected in elephant seals may serve to rectify gluconeogeneic PEP production during restricted anaplerotic inflow in these fasting-adapted animals.

Regulation of glucose turnover at the onset of exercise in the dog

1992 ◽  
Vol 72 (6) ◽  
pp. 2487-2494 ◽  
Author(s):  
P. D. Miles ◽  
D. T. Finegood ◽  
H. L. Lickley ◽  
M. Vranic
Keyword(s):  
Early Period ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Molar Ratio ◽  
Glucose Turnover ◽  
Abrupt Increase ◽  
Glucoregulatory Hormones ◽  
Exercise Period ◽  
Important Regulator

The early responses of endogenous glucose production (Ra), glucose utilization (Rd), and glucoregulatory hormones to moderate treadmill exercise (12% incline, 100 m/min, 60 min) were examined in dogs. Rd increased rapidly and progressively from the start of exercise. The change in Ra, as estimated with a variable-volume model of glucose kinetics, was biphasic, with an abrupt increase by 8.5 +/- 2.3 mumol.min-1.kg-1, followed by a delayed further increase that matched Rd 11–22 min after the onset of exercise. The plasma glucagon-to-insulin molar ratio fell slightly at the onset of exercise and then increased gradually. The glucagon-to-insulin ratio was correlated with Ra over the entire exercise period (r = 0.63, P less than 0.0001), but not during the early part of exercise, when Ra increased rapidly. The catecholamine- (epinephrine plus norepinephrine) to-insulin molar ratio was correlated with Ra during the early period (r = 0.52, P less than 0.01) and over the entire period of exercise (r = 0.66, P less than 0.0001). Our results confirm previous demonstrations that the glucagon-to-insulin molar ratio is an important regulator of Ra during exercise. We hypothesize that the catecholamine-to-insulin molar ratio is important during the early period of exercise and possibly during late exercise as an additional regulatory factor to the glucagon-to-insulin molar ratio.

scholarly journals Central effects of thyronamines on glucose metabolism in rats

2009 ◽  
Vol 201 (3) ◽  
pp. 377-386 ◽  
Author(s):  
Lars P Klieverik ◽  
Ewout Foppen ◽  
Mariëtte T Ackermans ◽  
Mireille J Serlie ◽  
Hans P Sauerwein ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Low Dose ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Central Administration ◽  
Stable Isotope Dilution ◽  
Glucoregulatory Hormones ◽  
The Central Nervous System

Thyronamines are naturally occurring, chemical relatives of thyroid hormone. Systemic administration of synthetic 3-iodothyronamine (T1AM) and – to a lesser extent – thyronamine (T0AM), leads to acute bradycardia, hypothermia, decreased metabolic rate, and hyperglycemia. This profile led us to hypothesize that the central nervous system is among the principal targets of thyronamines. We investigated whether a low dose i.c.v. infusion of synthetic thyronamines recapitulates the changes in glucose metabolism that occur following i.p. thyronamine administration. Plasma glucose, glucoregulatory hormones, and endogenous glucose production (EGP) using stable isotope dilution were monitored in rats before and 120 min after an i.p. (50 mg/kg) or i.c.v. (0.5 mg/kg) bolus infusion of T1AM, T0AM, or vehicle. To identify the peripheral effects of centrally administered thyronamines, drug-naive rats were also infused intravenously with low dose (0.5 mg/kg) thyronamines. Systemic T1AM rapidly increased EGP and plasma glucose, increased plasma glucagon, and corticosterone, but failed to change plasma insulin. Compared with i.p.-administered T1AM, a 100-fold lower dose administered centrally induced a more pronounced acute EGP increase and hyperglucagonemia while plasma insulin tended to decrease. Both systemic and central infusions of T0AM caused smaller increases in EGP, plasma glucose, and glucagon compared with T1AM. Neither T1AM nor T0AM influenced any of these parameters upon low dose i.v. administration. We conclude that central administration of low-dose thyronamines suffices to induce the acute alterations in glucoregulatory hormones and glucose metabolism following systemic thyronamine infusion. Our data indicate that thyronamines can act centrally to modulate glucose metabolism.

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.

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 adrenergic blockade on glucose kinetics in septic and burned guinea pigs

1981 ◽  
Vol 241 (3) ◽  
pp. R222-R227
Author(s):  
M. J. Durkot ◽  
R. R. Wolfe
Keyword(s):  
Guinea Pigs ◽  
Glucose Production ◽  
Constant Infusion ◽  
Adrenergic Blockade ◽  
Glucose Kinetics ◽  
Counterregulatory Hormones ◽  
Beta Adrenergic ◽  
Glucoregulatory Hormones ◽  
Adrenergic Blocker ◽  
Septic Group

We have used the primed-constant infusion of [6-3H]glucose to study the effects of phentolamine, an alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker, on glucose production and clearance in gastrostomy-fed control, septic (repeated sub-Q Escherichia coli injections), and burned (25-30% BSA) guinea pigs. Hypermetabolism and elevated glucoregulatory hormones were evident in both traumatized models, whereas their glucose kinetic response was different. Basal glucose production and clearance were elevated in the burned group and were depressed in the septic group when compared to control values. Propranolol caused a further increase in glucose production and clearance in the burned group, whereas it depressed glucose production and clearance to an even greater extent in the septic group. Phentolamine also produced an increase in glucose production and clearance in the burned group. In the septic group, phentolamine had no significant effect on glucose production, but clearance was significantly elevated. Thus, although alpha- or beta-adrenergic blockade normalized metabolic rate in both groups with respect to control animals, glucose kinetics remained different despite similar changes in counterregulatory hormones.

Autoregulation of Glucose Production

Physiology ◽  
2000 ◽  
Vol 15 (4) ◽  
pp. 198-202 ◽  
Author(s):  
Luc Tappy ◽  
Eric Jéquier ◽  
Philippe Schneiter
Keyword(s):  
Glucose Production ◽  
Glucose Sensing ◽  
Endogenous Glucose Production ◽  
Hepatic Glucose ◽  
Glucoregulatory Hormones ◽  
Endogenous Glucose ◽  
Stimulation Of

Glucose itself regulates endogenous glucose production independently of changes in glucoregulatory hormones. In addition, acute stimulation of gluconeogenesis does not increase net glucose production. This indicates autoregulation of glucose production. Glucokinase plays a role in this process by allowing hepatic glucose sensing.

The reliability of rates of glucose appearance in vivo calculated from single tracer injections

1979 ◽  
Vol 57 (11) ◽  
pp. 1267-1274 ◽  
Author(s):  
John R. Allsop ◽  
Robert R. Wolfe ◽  
Joseph J. DiStephano III ◽  
John F. Burke
Keyword(s):  
Plasma Glucose ◽  
Infusion Rate ◽  
Specific Radioactivity ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Constant Infusion ◽  
Glucose Turnover ◽  
Time Curve ◽  
The Mean

The rate of appearance of unlabelled glucose was calculated from changes in plasma glucose specific radioactivity after a single intravenous injection of labelled glucose and compared with the actual constant infusion rate of unlabelled glucose into an anaesthetized dog with all sources of endogenous glucose production surgically removed. The mean steady-state rate of appearance of unlabelled glucose calculated from the area under the specific radioactivity versus time curve was 7% higher than the actual infusion rate (n = 4), but the difference was not statistically significant. The variability in the rate calculated in this manner was, however, greater than the variability we have reported with rates determined from a primed constant infusion of tracer. Using 15- to 60- or 60- to 120-min specific radioactivity data the mean rate of appearance of glucose, calculated on the assumption of a one-pool model for glucose turnover in vivo, was approximately 60% higher than the actual infusion rate. The results also indicate that it is possible to construct multi-pool models, but it is difficult to equate specific physiological events with the individual terms of the multi-exponential equation which describes the changes in plasma glucose specific radioactivity.

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