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V A Hammond

Publications and source records attributed to V A Hammond.

9 recordsLinked to original sources
PubMed1987

Substrate cycling between triglyceride and fatty acid in human adipocytes.

Substrate cycles in metabolism require energy and generate heat, and they may be involved in thermogenesis. We have studied one such cycle between triglyceride and fatty acid in isolated human adipocytes using a nonisotopic technique. In the absence of added hormone, and with 5 mmol/L (90 mg/dL) glucose in the incubation medium, lipolysis and fatty acid reesterification coexisted such that 40 +/- 4% (mean +/- SEM) of the fatty acid produced was cycled back into triglyceride. In 51 individual subjects the range was from 0% to 100%. Both lipolysis and the quantity of fatty acid recycled correlated positively with cell volume (P less than .001 and P less than .005, respectively). Norepinephrine (10(-6) mol/L) alone (33 experiments) increased lipolysis 3.1-fold, and reduced the percentage of fatty acid reesterified. Cycling was similar to that in the basal state. Lipolysis was inhibited 46% by postabsorptive levels of insulin alone (18 experiments), but the proportion of fatty acid reesterified increased such that the quantity cycled back into triglyceride was similar to that observed in the basal state. In the presence of both norepinephrine and insulin (18 experiments), lipolysis was increased by 58% while 31 +/- 4% of the fatty acid released was reesterified. In consequence, the quantity of fatty acid cycled back into triglyceride increased 2.1-fold. Increasing the insulin level fivefold or the medium glucose concentration to 20 mmol/L produced no further increase in the quantity of fatty acid reesterified. A substrate cycle exists, therefore, between triglyceride and fatty acid in human adipose tissue, and its activity is modified by norepinephrine and insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1986

Effects of monensin on insulin interactions with isolated hepatocytes. Evidence for inhibition of receptor recycling and insulin degradation.

Recent evidence suggests that, during endocytosis, receptors for many polypeptide ligands are spared degradation and are recycled to the plasma membrane for re-utilization. The univalent ionophore monensin was shown to inhibit membrane recycling. We therefore examined its effects on insulin interactions with isolated rat hepatocytes to characterize further receptor endocytosis and recycling in these cells. At 10 degrees C, in the absence of endocytosis, no change in insulin binding was observed. However, at 37 degrees C a concentration-dependent decrease in 125I-insulin binding was seen in the presence of insulin; this reached a maximum of 60% at 1 nM-insulin. Competitive binding studies showed this to be due to a 50-60% decrease in cell-surface insulin-receptor concentration, although the total cellular receptor concentration remained unchanged, suggesting that monensin causes the intracellular sequestration of receptors. Time-course studies of the processing of 2.5 nM-insulin showed that monensin produced a 50-60% decrease in surface binding, accompanied by a similar decrease in internalization and total inhibition of insulin degradation. When hepatocytes with 125I-insulin prebound to their surface receptors at 10 degrees C were warmed to 37 degrees C, monensin had no effect on internalization, but caused marked impairment of intracellular insulin degradation. It is concluded that monensin inhibits receptor recycling and cellular insulin degradation.

Animals↗
PubMed1984

The metabolic effects of dopamine in man.

The metabolic effects of dopamine have been investigated by its infusion in normal man with and without simultaneous somatostatin administration. Dopamine was infused into overnight fasted men at 1.5 microgram/kg/min (n = 6) and 3.0 micrograms/kg/min (n = 5) for 120 min. Plasma dopamine concentrations at 120 min were 78 +/- 9 nmol/l and 117 +/- 17 nmol/l respectively, associated with a marginal rise in plasma noradrenaline. Dopamine (1.5 microgram/kg/min) induced an early and sustained rise in plasma glucagon (48 +/- 9 pg/ml versus 19 +/- 6 pg/ml in saline controls at 10 min, p less than 0.01) and a transient elevation in serum growth hormone which peaked to 17.7 (range 4.5-71.8) mU/l at 60 min (7.2 (range 0.6-37.7) mU/l with saline, p less than 0.05) but did not alter serum insulin, blood glucose or other metabolite levels. At 3.0 micrograms/kg/min, dopamine in addition provoked mild and transient elevations in blood glucose and serum insulin. Somatostatin (250 micrograms/h) suppressed circulating insulin, glucagon, and growth hormone levels and abolished the small hyperglycaemic effect seen with the higher dopamine dose. Somatostatin alone induced a progressive rise in circulating non-esterified fatty acid and 3-hydroxybutyrate levels reflecting insulin deficiency. This rise in NEFA and 3-hydroxybutyrate was increased by dopamine particularly at the higher dosage (plasma NEFA; somatostatin alone, 1.08 +/- 0.13 mmol/l; somatostatin plus dopamine 3 micrograms/kg/min, 1.44 +/- 0.17 mmol/l at 120 min, p less than 0.01: blood 3-hydroxybutyrate; somatostatin alone, 0.32 +/- 0.04 mmol/l; somatostatin plus dopamine 3 micrograms/kg/min, 0.56 +/- 0.12 mmol/l at 120 min, p less than 0.05). Thus: 1) dopamine at pharmacological dosage has minor effects when other endocrine mechanisms are intact, 2) it enhances lipolysis and ketogenesis during somatostatin-induced insulin deficiency; 3) the hyperglycaemia effect of the higher dopamine dose is probably mediated through stimulated glucagon secretion.

3-Hydroxybutyric Acid↗
PubMed1982

The effects of metabolic acidosis in vivo on insulin binding to isolated rat adipocytes.

Insulin resistance in vivo and impaired insulin binding to isolated adipocytes are characteristic of diabetic ketoacidosis in the rat. To determine the respective roles of diabetes and acidaemia in the genesis of the binding defect, insulin binding to adipocytes from alkali-treated ketoacidotic diabetic and ammonium chloride acidotic rats was studied. Reversal of the acidaemia of ketoacidotic rats by sodium bicarbonate infusion (pH 6.73 +/- 0.027 to 7.35 +/- 0.027, p less than 0.001, n = 12) increased adipocyte insulin binding (0.51 +/- 0.21% to 2 x 10(5) cells/ml, n = 6 untreated versus 1.10 +/- 0.27% to 2 x 10(5) cell, n = 6 treated, p less than 0.05). Scatchard analysis showed this to be due to an increase in insulin receptor concentration. Ammonium chloride infusion caused marked metabolic acidaemia (pH 6.72 +/- 0.04, n = 12) and insulin binding to adipocytes was markedly decreased (0.81 +/- 0.12% to 2 x 10(5) cells/ml n = 6 versus 2.40 +/- 0.22% to 2 x 10(5) cells/ml, n = 6 in controls p less than 0.02), due to a change in receptor concentration. The apparent affinity of the receptor was markedly decreased in diabetic animals compared with normal controls but was unchanged in ammonium chloride acidotic animals. Thus in diabetic ketoacidosis there is both decreased affinity and number of insulin receptors partially reversible by prolonged alkali infusion. Only changes in affinity appeared to be specific for the diabetic state.

Acidosis↗