Ketoacidosis in Pancreatectomized Man

Aj, Barnes; Goerge, K; Gm, Alberti; Smythe, P.; Fp, Alford; Dj, Chisholm

doi:10.1056/nejm197706022962202

Cited by 96 publications

(41 citation statements)

References 30 publications

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“…It has been suggested that hyperglucagonemia is essential for maximal ketogenesis (1). This hypothesis is consistent with the observations of the present study as well as those studies in which glucagon-deficient diabetic patients developed less hyperketonemia than nonglucagon-deficient diabetic patients (16,38). However, in studies using rat livers perfused in vitro, it has been reported that glucagon does not augment maximal rates of ketogenesis produced by -2 mM oleate but does increase ketogenesis at submaximal FFA concentrations (9).…”

Section: Discussionsupporting

confidence: 92%

Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man.

Miles¹,

et al. 1983

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A B S T R A C T The present studies were undertaken to assess the relative effects of free fatty acid (FFA) availability, glucagon excess, and insulin deficiency on ketone body (KB) production in man. To determine whether an increase in FFA availability would augment KB production in the absence of insulin deficiency and glucagon excess, plasma insulin and glucagon were maintained at basal concentrations by infusion of somatostatin and exogenous insulin and glucagon, and plasma FFA were increased from 0.32±0.06 to 1.4±0.1 mM by a 2.5-h-infusion of a triglyceride emulsion plus heparin. KB production increased fivefold from 2.2±0.4 to 11.4±1.2 ,umol * kg-' e min-', P < 0.001. To determine whether insulin deficiency would further augment KB production, analogous experiments were performed but the replacement infusion of insulin was stopped. Despite a greater increase in plasma FFA (from 0.26±0.04 to 1.95±0.3 mM), KB production increased (from 1.5±0.3 to 11.1±1.8 Amol-kg-'min-') to the same extent as in the absence of insulin deficiency. To determine whether hyperglucagonemia would augment KB production beyond that accompanying an increase in plasma FFA and, if so, whether this required insulin deficiency, similar experiments were performed in which the glucagon infusion rate was increased to produce plasma glucagon concentrations of 450-550 pg/ml with and without maintenance of the basal insulin infusion. When basal plasma insulin concentrations were maintained, hyperglucagonemia did not further increase KB production; however, when the basal insulin infusion was discontinued, hyperglucagonemia increased KB production significantly, whereas no change was observed in saline control experiments. These studies indicate that, in man, FFA availability is a major

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Section: Discussionsupporting

confidence: 92%

Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man.

Miles¹,

et al. 1983

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“…Thuis, the glycemic response to hyperglucagonemi-ia was 5-15 times greater in insuilin-withdrawn diabetics than in normal subjects (2). More recent studies comparing painereatectonmized man and juvenile-onset diabetics indicate that endogenous hyperglucagonemia worsens the hyperglycemia and ketonemia that accompany insulini deficiency (3). Augmented sensitivity to the hyperglycemic effects of glucagon has also been reported in uremics (29).…”

Section: Discussionmentioning

confidence: 98%

“…In this regard the studies indicating estrogen stimulation of prolactin receptors (35) and induction of luteinizing hormone receptors in the granulosa cells of the ovary by follicle-stimulating hormone (36) are of great interest. Regardless of the mechanism involved, increased glucagon binding, coupled with augmented basal and glucagon-stimulated adenylate cyclase activity in insulin-deprived diabetic rats, may provide a cellular basis for the increased glycemic and ketonemic response to glucagon in insulin-deprived diabetics (2,3).…”

Section: Discussionmentioning

confidence: 99%

Glucagon Binding and Adenylate Cyclase Activity in Liver Membranes from Untreated and Insulin-Treated Diabetic Rats

Soman¹,

Felig²

1978

J. Clin. Invest.

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“…The relatively benign metabolic decompensation of patient 2 after 3 d of insulin withdrawal supports the view that this form of diabetes might, in fact, be less prone to ketosis than juvenile onset-type diabetes. Similarly, Barnes et al (39) showed a much slower rise in blood glucose and ketone bodies in pancreatectomized patients after insulin deprivation than in juvenile-type diabetics, which reflects the slowed onset of ketoacidosis in the juvenile-type diabetics of Gerich et al (40) during glucagon suppression by somatostatin. The administration of glucagon accelerated the development of ketoacidosis back to where it was before somatostatin administration (40).…”

Section: Discussionmentioning

confidence: 89%

Glucagon Immunoreactivities and Amino Acid Profile in Plasma of Duodenopancreatectomized Patients

Müller¹,

Berger²,

Suter³

et al. 1979

J. Clin. Invest.

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A B S T R A C T Glucogon immunoreactivity (IRG) was measured in plasma of duodenopancreatectomized subjects with a nonspecific (K-4023) and a specific (30-K) glucagon antiserum. After an overnight fast, plasma IRG (K-4023) was significantly (P < 0.05) higher in the subjects without pancreas, averaging 782±79 (SEM) pgeq/ml, than in the controls (482±80 pgeq/ml). IRG (30-K) of 162±68 pglml did not change during an infusion ofarginine (450 mg/kg per 40 min). Insulin deprivation during 3 d in one patient did not restore the IRG response to arginine as reported in depancreatized dogs.Bio-Gel P-30 column chromatography revealed that virtually all IRG (30-K) measured in whole plasma was of different molecular weight than glucagon, and primarily of a mol wt 2 40,000. Intravenous arginine did not significantly alter the chromatographic pattern of these plasmas. Thus, as postulated by others, duodenopancreatectomized humans have virtually no circulating 3,500-dalton glucagon. Hence, the presence of 3,500-dalton glucagon in plasma is not a condition for the diabetic state. It might, nevertheless, when present in normal or excessive amounts, worsen the metabolic state of diabetic patients.Among 14 amino acids measured in plasma of these patients, the concentrations of alanine, serine, ornithine, and arginine were significantly (P < 0.05) elevated to approximately twice that of normal: alanine and serine are both substrates for gluconeogenesis, whereas ornithine and arginine are involved in the formation of urea, the second product of hepatic gluco-

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Ketoacidosis in Pancreatectomized Man

Cited by 96 publications

References 30 publications

Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man.

Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man.

Glucagon Binding and Adenylate Cyclase Activity in Liver Membranes from Untreated and Insulin-Treated Diabetic Rats

Glucagon Immunoreactivities and Amino Acid Profile in Plasma of Duodenopancreatectomized Patients

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