Rapid Conversion by Insulin of Hepatic Intermediary Metabolism from Glucose Production to Glucose Utilization in the Liver of Alloxan-diabetic Rats

Seitz, Hans; Müller, M.J.; Krone, Wilhelm; Tarnowski, W.

doi:10.2337/diab.26.12.1159

Cited by 23 publications

(9 citation statements)

References 15 publications

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“…Furthermore, even if free fatty acid and amino acid concentrations were markedly different, we do not know whether the effects would be rapid enough to cause the increase in insulin need that was evident within the first hour after ingestion of the mixed meal. Amino acids and free fatty acids are known stimulants of gluconeogenesis (42)(43)(44)(45)(46), and higher insulin concentrations are required to suppress gluconeogenesis than glycogenolysis (47)(48)(49). Therefore, the protein and fat contained within the mixed meal may have increased the amount of insulin required to suppress glucose production.…”

Section: Discussionmentioning

confidence: 99%

Effects of Nonglucose Nutrients on Insulin Secretion and Action in People With Pre-Diabetes

et al. 2007

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To determine whether nonglucose nutrient-induced insulin secretion is impaired in pre-diabetes, subjects with impaired or normal fasting glucose were studied after ingesting either a mixed meal containing 75 g glucose or 75 g glucose alone. Despite comparable glucose areas above basal, glucose-induced insulin secretion was higher (P < 0.05) and insulin action lower (P < 0.05) during the meal than the oral glucose tolerance test (OGTT) in all subgroups regardless of whether they had abnormal or normal glucose tolerance (NGT). However, the nutrientinduced ␦ (meal minus OGTT) in insulin secretion and glucagon concentrations did not differ among groups. Furthermore, the decrease in insulin action after meal ingestion was compensated in all groups by an appropriate increase in insulin secretion resulting in disposition indexes during meals that were equal to or greater than those present during the OGTT. In contrast, disposition indexes were reduced (P < 0.01) during the OGTT in the impaired glucose tolerance groups, indicating that reduced glucose induced insulin secretion. We conclude that, whereas glucose-induced insulin secretion is impaired in people with abnormal glucose tolerance, nonglucose nutrient-induced secretion is intact, suggesting that a glucosespecific defect in the insulin secretory pathway is an early event in the evolution of type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Effects of Nonglucose Nutrients on Insulin Secretion and Action in People With Pre-Diabetes

et al. 2007

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“…Rapid alterations of intrahepatic metabolic intermediates, cofactors, and regulatory enzymes are essential controlling events that permit the liver's transition from a glucose-producing organ during starvation to an organ capable of net carbohydrate uptake during alimentation (15,33,34,38). This change is essential for the control of blood glucose levels, and for the replenishment of hepatic glycogen stores.…”

Section: Discussionmentioning

confidence: 99%

Hepatic and Cerebral Energy Metabolism after Neonatal Canine Alimentation

1983

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Summaryduration than older rats (13,14). In other investigations amongIntrahepatic and intracerebral metabolic responses to neonatal fasting or enteric carbohydrate alimentation were investigated among newborn dogs. Pups were either fasted or given an intravenous glucose infusion (alimented) before an enteric feeding of physiologic quantities of either glucose or galactose. These pups were also compared to another group which was completely starved throughout the study period. Gastrointestinal carbohydrate feeding resulted in enhanced hepatic glycogen content among pups after a prior state of fasting. Though there were no differences of glycogen content between glucose or galactose feeding in this previously fasted group, combined intravenous glucose and enteric galactose administration produced the greatest effect on hepatic glycogen synthesis. Intrahepatic fructose 1, 6-diphosphate and phosphoenolpyruvate levels were increased among previously fasted pups fed enteric monosaccharides compared to completely starved control pups, whereas intrahepatic phosphoenolpyruvate and pyruvate levels were elevated after combined intravenous and enteric carbohydrate administration. Of greater interest was the observation that hepatic levels of ATP were significantly elevated among all groups given exogenous carbohydrates compared to the completely starved control group. In contrast to the augmented hepatic glycogen and ATP levels, there were no alterations of cerebral glycogen or ATP after alirnentation. Nevertheless, cerebral pyruvate and/or phosphoenolpyruvate concentrations were elevated after enteric or combined intravenous and enteric alimentation compared to the totally starved control pups. newborn piglets, starvation was associated with a decreased b a d metabolism rate as evident by diminished rates of oxygen consumption (9).Past experience among human newborn infants has demonstrated that early alimentation prevents fasting hypoglycemia and improves neonatal survival (1, 6, 43). Additionally, alimentation of newborn rats results in stable blood glucose concentrations and glucose production rates and also augments circulating alternate fuels levels (1 1, 12).Rapid alterations of intrahepatic metabolic intermediates, cofactors, and regulatory enzymes are essential controlling events that permit the liver's transition from a glucose-producing organ during starvation to an organ capable of net carbohydrate uptake during alimentation (15,33,34,38). This change is essential for the control of blood glucose levels, and for the replenishment of hepatic glycogen stores. During carbohydrate alimentation pyruvate becomes the predominant source of acetyl-CoA for the tricarboxylic acid cycle and may result in enhanced ATP production. The transition from fasting hepatic intermediary metabolism to that of an alimented state has been well documented among adult mammals. As there are little in vivo data describing the regulation of intrahepatic metabolism among fasted neonates, or the response of the neonatal liver to subsequent al...

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“…The methods for the determination ofstandard clinical and laboratory parameters, of glucose, lactate, pyruvate, glycerol, alanine, a-amino-N, free fatty acids (FFA), ofthe hormones insulin and glucagon, of pH, p02, and PCO2 as well as of the specific activity of glucose have been described in detail previously (15,16,18,19 -(pVdc/dt), where c is the concentration of glucose, V represents the glucose distribution volume (calculated from the initial decline in the specific activity of glucose after the primed injection of the tracer), and p is the pool fraction (0.65 according to [21]). Polynomial curves were fitted to the SA and plasma concentrations of glucose vs. time curves and a smoothing tricubic spline algorithm was used for this purpose on a TR 440 Telefunken computer.…”

Section: Methodsmentioning

confidence: 99%

Effect of ketone bodies on glucose production and utilization in the miniature pig.

Müller¹,

Paschen²,

Seitz³

1984

J. Clin. Invest.

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As bstract. The effect of ketone bodies on glucose production (Ra) and utilization (Rd) was investigated in the 24-h starved, conscious unrestrained miniature pig. Infusing Na-DL-3-OH-butyrate (Na-DL-f-OHB) and thus shifting the blood pH from 7.40 to 7.56 resulted in a decrease of Ra by 52% and of Rd by 45%, as determined by the isotope dilution technique. Simultaneously, the concentrations of arterial insulin and glucagon were slightly enhanced, whereas the plasma levels of glucose, lactate, pyruvate, alanine, a-amino-N, and free fatty acids (FFA) were all reduced. Infusion ofNa-bicarbonate, which yielded a similar shift in blood pH, did not mimick these effects. Infusion of equimolar amounts of the ketoacid, yielding a blood pH of 7.35, induced similar metabolic alterations with respect to plasma glucose, Ra, Rd, and insulin; however, plasma alanine and a-amino-N increased.Infusing different amounts of Na-DL-3-OHB resulting in plasma steady state levels of ketones from 0.25 to 1.5 mM had similar effects on arterial insulin and glucose kinetics. No dose dependency was observed.Prevention of the Na-DL-3-OHB-induced hypoalaninemia by simultaneous infusion of alanine (1 ttmol/kg X min) did not prevent hypoglycemia.Infusion of Na-DL-l-OHB plus insulin (0.4 mU/kg in plasma glucose and Ra; however, on infusion of somatostatin plus Na-DL-3-OHB, hypoglycemia and the reduced Ra were maintained.In the anaesthetized 24-h starved miniature pig, Na-DL-3-OHB infusion decreased the hepatic exchange for glucose, lactate, and FFA, whereas the exchange for glycerol, alanine, and a-amino-N as well as liver perfusion rate were unaffected. Simultaneously, portal glucagon and insulin as well as hepatic insulin extraction rate were elevated. Leg exchange for glucose, lactate, glycerol, alanine, a-amino-N, and FFA were decreased, while ketone body utilization increased.Repeated infusion of Na-DL-3-OHB at the fourth, fifth, and sixth day of starvation in the conscious, unrestrained mini-pig resulted in a significant drop in urinary nitrogen (N)-excretion. However, this effect was mimicked by infusing equimolar amounts of Na-bicarbonate. In contrast, when only the ketoacid was given, urinary Nexcretion accelerated.To summarize: (a) Ketone bodies decrease endogenous glucose production via an insulin-dependent mechanism; in addition, ketones probably exert a direct inhibitory action on gluconeogenesis. The ketone bodyinduced hypoalaninemia does not contribute to this effect. (b) The counterregulatory response to hypoglycemia is reduced by ketones. (c) As a consequence of the decrease in Ra, glucose utilization declines during ketone infusion.(d) The insulin-stimulated MCR for glucose is not affected by ketones. (e) Ketones in their physiological moiety do not show a protein-sparing effect.

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Rapid Conversion by Insulin of Hepatic Intermediary Metabolism from Glucose Production to Glucose Utilization in the Liver of Alloxan-diabetic Rats

Cited by 23 publications

References 15 publications

Effects of Nonglucose Nutrients on Insulin Secretion and Action in People With Pre-Diabetes

Effects of Nonglucose Nutrients on Insulin Secretion and Action in People With Pre-Diabetes

Hepatic and Cerebral Energy Metabolism after Neonatal Canine Alimentation

Effect of ketone bodies on glucose production and utilization in the miniature pig.

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