Conversion of Dl-Lactate-2-C14 or -3-C14 or Pyruvate-2-C14 to Blood Glucose in Humans: Effects of Diabetes, Insulin, Tolbutamide, and Glucose Load*

221

A B S T R A C T The aim of the present experiments was to determine the effects of basal glucagon on glucose production after induction of prolonged insulin lack in normal conscious dogs fasted overnight. A selective deficiency of insulin or a combined deficiency of both pancreatic hormones was created by infusing somatostatin alone or in combination with an intraportal replacement infusion of glucagon. Glucose production (GP) When insulin deficiency was induced in the presence of basal glucagon the latter hormone caused GP to double and then to decline so that after 4 h it had returned to the control rate. The conversion of alanine and lactate into glucose, on the other hand, increased throughout the period of insulin lack. Withdrawal of glucagon after GP had normalized resulted in a 40% fall in GP, a 37% decrease in GNG, and a marked decrease in the plasma glucose concentration. Induction of insulin deficiency in the absence of basal glucagon resulted in an initial (30%) drop in GP followed by a restoration of normal GP after 2-3 h and moderately enhanced glucose formation from alanine and lactate.It can be concluded that (a) the effect of relative hyperglucagonemia on GP is short-lived; (b) the waning of the effect of glucagon is attributable solely to a diminution of glycogenolysis because GNG remains stimulated; (c)

Section: Resultssupporting

confidence: 92%

Effect of glucagon on glucose production during insulin deficiency in the dog.

Cherrington¹,

Lacy²,

Chiasson³

1978

221

“…Firstly, significantly greater net splanchnic uptakes of lactate and pyruvate were observed in the diabetic group suggesting an increase in Cori cycle activity. This observation agrees well with the findings of increased conversion of lactate-"C and pyruvate-14C into blood glucose in diabetic patients (17,18), whereas lactate conversion to C02 is reduced (19). The source of the extra lactate and pyruvate generated for heightened Cori cycle activtiy in the diabetics is not, however, readily apparent, inasmuch as peripheral output of these metabolites was not increased nor were arterial levels reduced.…”

Section: Introductionsupporting

confidence: 90%

Splanchnic and peripheral glucose and amino acid metabolism in diabetes mellitus

Wahren¹,

Felig²,

Cerasi³

et al. 1972

308

132

A B ST R A CT Splanchnic and leg exchange of glucose, lactate, pyruvate, and individual plasma amino acids was studied in diabetics 24 hr after withdrawal of insulin and in healthy controls. Measurements were made in the basal postabsorptive state and during the administration of glucose at a rate of 2 mg/kg per min for 45 min.In the basal state, net splanchnic glucose production did not differ significantly between diabetics and controls. However, splanchnic uptake of alanine and other glycogenic amino acids was 11-2 times greater in the diabetics, while lactate and pyruvate uptake was increased by 65-115%. Splanchnic uptake of these glucose precursors could account for 32% of hepatic glucose output in the diabetics, as compared to 20% in the controls. This increase in precursor uptake was a consequence of a two-to threefold increment in fractional extraction of these substrates inasmuch as arterial levels of alanine, glycine, and threonine were reduced in the diabetics, while the levels of the remaining substrates were similar in the two groups. Peripheral output of alanine and other glycogenic amino acids as reflected in arterio-femoral venous differences was similar in both groups. An elevation in arterial valine, leucine, and isoleucine was observed in the diabetics, but could not be accounted for on the basis of altera- Administration of glucose (2 mg/kg per min) for 45 min resulted in an 80% reduction in splanchnic glucose output in controls, but failed to inhibit hepatic glucose release in the diabetics despite a twofold greater increment in arterial glucose levels. In both groups no consistent changes in arterial glucagon were observed during the infusion.It is concluded that in nonketotic diabetics (a) total splanchnic output of glucose is comparable to controls, but the relative contribution of gluconeogenesis may be increased by more than 50%; (b) accelerated splanchnic uptake of glucose precursors is a consequence of increased hepatic extraction of available substrates rather than a result of augmented substrate supply; and (c) the failure of glucose infusion to inhibit hepatic glucose output suggests that the exquisite sensitivity of the liver to the infusion of glucose in normal man is a consequence of glucose-induced insulin secretion. INTRODUCTIONThe contribution of altered hepatic glucose balance to the metabolic defect in diabetes mellitus has long been the subject of inquiry and debate. Numerous investigations employing the hepatic venous catheter technique (2, 3), or isotope dilution methods (4-6), have provided data on the net rate of hepatic glucose release and on systemic glucose turnover in diabetic patients. Little is known, however, about the effect of diabetes on the hepatic uptake and peripheral release of glucose precursors. Specifically, the question of whether an augmentation in substrate availability or alterations in

“…1The uniformly labeled isotope is not diluted by glucose formed in the liver by the recycling of glucose through lactate (13,14). In this paper, the term "glucose turnover" refers to new, nonrecycled glucose derived from nonlabeled precursors.…”

Section: Preliminary Examination Of Tracer Technicsmentioning

confidence: 99%

Glucose Turnover and Disposal in Maturity-Onset Diabetes

Bowen¹,

Moorhouse²

1973

A B S T R A C T The glucose turnover rate in maturityonset diabetes in man has been variously reported as increased, normal, and decreased. The present experiments suggest that these discrepancies may have been due to methodology, and to nonrecognition of a circadian cycle in the glucose turnover rate that is present in health, and marked in diabetes.During the early morning hours the glucose turnover rate in maturity-onset diabetes is increased in proportion to the fasting blood glucose level. It may reach three to four times the rate found in health. During the evening hours the increments are about one-half as great.The glucose outflow rate constant, k, lower in diabetes than in health, is also lower in both groups in the evening than in the morning.An analysis of the relative contributions of glucose overproduction and underutilization to the development of hyperglycemia in maturity-onset diabetes indicates that overproduction is the greater factor. The relative role of underutilization appears to increase as the fasting blood glucose level increases.The circulating glucose oxidation rate in maturityonset diabetes is only slightly lower than in health, but the fraction oxidized is markedly lower, and only a small fraction is excreted.The principal conclusion is that in maturity-onset diabetes there is a hypertrophied flux of endogenous glucose, most of which is neither oxidized nor excreted. The precursors and the qualitative and quantitative metabolic fates of this excess glucose are unknown.