Importance of basal glucagon in maintaining hepatic glucose production during a prolonged fast in conscious dogs

Hendrick, G. K.; Wasserman, David H.; Frizzell, R. T.; Williams, Phillip E.; Lacy, D. Brooks; Jaspan, J. B.; Cherrington, Alan D.

doi:10.1152/ajpendo.1992.263.3.e541

Cited by 13 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fasted dogs, acute suppression of glucagon secretion by an infusion of somatostatin and insulin to maintain basal insulin concentrations decreased EGP and the conversion of gluconeogenic precursors to plasma glucose, while simultaneously increasing hepatic glycogen content [33]. A similar observation was made in dogs infused for 3 days with stress hormones when glucagon infusion was abruptly stopped and the infusions of cortisol, epinephrine and growth hormone were continued [34]. Interestingly, neither fructose nor hyperglucagonaemia alone produced such effects.…”

Section: Discussionmentioning

confidence: 68%

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects

et al. 1996

View full text Add to dashboard Cite

SummaryIncreased endogenous glucose production (EGP) and gluconeogenesis contribute to the patho-genesis of hyperglycaemia in non-insulin-dependent diabetes mellitus (NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of fructose increases EGP in obese NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13 C fructose (0.3 g · kg fat free mass -1 · h -1 ) for 3 h. Fructose failed to increase EGP (measured with 6,6 2 H glucose) in NIDDM (17.7 ± 1.9 µmol · kg fat free mass -1 · min -1 basal vs 15.9 ± 0.9 after fructose), in obese non-diabetic subjects (12.1 ± 0.5 basal vs 13.1 ± 0.5 after fructose) and in lean healthy subjects (13.3 ± 0.5 basal vs 13.8 ± 0.6 after fructose) although 13 C glucose synthesis contributed 73.2 % of EGP in lean subjects, 62.6 % in obese non-diabetic subjects, and 52.8 % in obese NIDDM patients. Since glucagon may play an important role in the development of hyperglycaemia in NIDDM, healthy subjects were also studied during 13 C fructose ingestion + hyperglucagonaemia (232 ± 9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8 % with ingestion of fructose + glucagon (p < 0.05) but remained unchanged during administration of fructose or glucagon alone. The plasma 13 C glucose enrichment was identical after fructose ingestion both with and without glucagon, indicating that the contribution of fructose gluconeogenesis to the glucose 6-phosphate pool was identical in these two conditions. We concluded that during fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of glucose 6-phosphate production from fructose and from other sources (i. e. glycogenolysis + gluconeogenesis from non-fructose precursors). [Diabetologia (1996) Abbreviations: EGP, Endogenous glucose production ; CHO, carbohydrate ; APE, atom percent excess ; GRd, glucose rate of disappearance ; FFM, fat-free mass.In healthy human subjects and in normal dogs, endogenous glucose production (EGP) has been shown not to rise when gluconeogenic substrates are infused and gluconeogenesis is increased [1][2][3][4][5]. This constancy of EGP was also observed during infusions of lactate [2] or fructose [5] when insulin and glucagon were maintained constant by infusions of somatostatin, insulin and glucagon, indicating autoregulation. The mechanisms responsible for this autoregulation of EGP may involve inhibition of gluconeogenesis from endogenous substrates [3] and/or of glucogenolysis [2] and stimulation of glycogen synthesis [5]. In non-insulin-depende...

show abstract

Section: Discussionmentioning

confidence: 68%

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects

et al. 1996

View full text Add to dashboard Cite

show abstract

“…At rest, glucagon stimulates glucose output resulting from increases in both glycogenolysis and gluconeogenesis (Beuers and Jungermann 1990;Cherrington et al, 1981;Hendrick et al, 1992;Jiang and Zhang, 2003;Stevenson et al, 1987).…”

Section: Role Of Glucagon During Exercisementioning

confidence: 99%

Glucagon Receptors: Effect of Exercise and Fasting

Lavoie

2005

Can. J. Appl. Physiol.

View full text Add to dashboard Cite

One paradox of hormonal regulation during exercise is the maintenance of glucose homeostasis after endurance training despite a lower increase in plasma glucagon. One explanation could be that liver sensitivity to glucagon is increased by endurance training. Glucagon exerts its effect through a 62 KDa glycoprotein receptor, member of the G protein-coupled receptor. To determine whether changes with exercise in glucagon sensitivity occurred at the level of the glucagon receptor (GR), binding characteristics of hepatic glucagon receptors were ascertained in rat purified plasma membranes. Saturation kinetics indicated no difference in the dissociation constant or affinity of glucagon receptor, but a significantly higher glucagon receptor binding density in liver in endurance trained compared to untrained animals. Along with endurance training, it appears that fasting also changes GR binding characteristics. In animals fasting 24 hrs, a significant increase in glucagon receptor density was also reported. Although the exact mechanism remains unknown, there is no doubt that the liver can adapt to physiological stress through modulation of GR binding characteristics to enhance the hepatic glucose production responsiveness to glucagon.

show abstract

“…The dogs, which are accustomed to being fed one meal daily, require nearly 18 h for absorption of the chow and meat diet (6). In the dog, hepatic glycogen stores are high after 18 h of fasting (11), and the liver is a net E293 producer of lactate, a sign of being in the fed or very early fasted state (6). In contrast, hepatic glycogen reserves in the rat are markedly depleted after an overnight fast, and the liver is a net consumer of lactate (9,17,30,42).…”

Section: Arterial Blood Concentrations Net Hepatic and Renal Uptakmentioning

confidence: 99%

Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs

Moore¹,

Satake²,

Baranowski

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

. Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs. Am J Physiol Endocrinol Metab 282: E286-E296, 2002; 10.1152/ajpendo.00201. 2001.-We tested the hypothesis that the loss of hepatic nerves decreases peripheral insulin sensitivity. Surgical hepatic denervation (DN) was performed in 22 dogs ϳ16 days before study; 7 dogs (Sham-Sal) had a sham procedure. A euglycemic hyperinsulinemic (1 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ; arterial insulin 35 Ϯ 1 U/ml in all dogs) clamp was performed in conscious dogs. From 0 to 90 min of the clamp, all dogs received the same treatment; then the DN dogs were divided into three groups. From 90 to 180 min, DN-PeA (n ϭ 7) and DN-PoA (n ϭ 7) groups received acetylcholine 2.5 g ⅐ kg Ϫ1 ⅐ min Ϫ1 via peripheral or portal vein, respectively, and DN-Sal (n ϭ 8) received no acetylcholine. During 150-180 min, the Sham-Sal, DN-Sal, DN-PeA, and DN-PoA groups exhibited glucose infusion rates of 12.4 Ϯ 0.8, 9.3 Ϯ 0.8 (P Ͻ 0.05 vs. Sham-Sal), 9.1 Ϯ 0.1 (P Ͻ 0.05 vs. ShamSal), and 12.7 Ϯ 1.6 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ; nonhepatic glucose uptakes of 11.5 Ϯ 0.9, 8.9 Ϯ 0.7 (P Ͻ 0.05 vs. Sham-Sal), 8.6 Ϯ 0.9 (P Ͻ 0.05 vs. Sham-Sal), and 11.9 Ϯ 1.7 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ; net hindlimb glucose uptakes of 18.4 Ϯ 2.1, 13.7 Ϯ 1.1 (P Ͻ 0.05 vs. Sham-Sal), 17.5 Ϯ 1.9, and 16.7 Ϯ 3.2 mg/min; and glucose utilization rates of 14.4 Ϯ 1.4, 10.4 Ϯ 0.8 (P Ͻ 0.05 vs. Sham-Sal), 9.8 Ϯ 0.9 (P Ͻ 0.05 vs. Sham-Sal), and 13.6 Ϯ 1.8 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 , respectively. DN caused peripheral insulin resistance, and intraportal but not peripheral acetylcholine restored insulin sensitivity. hepatic nerves; acetylcholine HEPATIC DENERVATION has been reported to result in peripheral insulin resistance in both rats and cats (49-51). The insulin resistance, which can be localized primarily to skeletal muscle (50), is reversible by intraportal, but not peripheral, infusion of acetylcholine (49) or a nitric oxide donor (35). This has led Lautt (19) to propose that insulin stimulates a hepatic parasympathetic reflex. According to this hypothesis, the reflex involves the release of acetylcholine, which binds to muscarinic receptors and stimulates the production of nitric oxide within the liver. As a result, the liver releases a humoral factor termed the hepatic insulinsensitizing substance, or HISS, that sensitizes skeletal muscle to insulin or has a direct insulin-like action (19). Although this is a very intriguing suggestion, the studies upon which it is based were performed in acutely denervated anesthetized animals under nonsteady-state conditions with the use of bolus injections of insulin. Therefore, the relevance of these findings to stable, conscious animals receiving physiological amounts of insulin remains to be established.We designed the current studies to test the hypothesis that loss of the hepatic nerves would impair peripheral glucose disposal under carefully controlled hormonal conditions in a physiological model. Specifically, we examined the response of conscious dogs ϳ16 days after hepatic denervation, u...

show abstract

Importance of basal glucagon in maintaining hepatic glucose production during a prolonged fast in conscious dogs

Cited by 13 publications

References 23 publications

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects

Effects of ingested fructose and infused glucagon on endogenous glucose production in obese NIDDM patients, obese non-diabetic subjects, and healthy subjects

Glucagon Receptors: Effect of Exercise and Fasting

Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs

Contact Info

Product

Resources

About