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Biomedical subjects

B Zinman

Publications and source records attributed to B Zinman.

At least 163 records · Page 9Linked to original sources

The metabolic and hormonal responses to glucose infusion in anaesthetized normal and diabetic dogs controlled by an artificial B-cell.

The metabolic response to glucose infusion in anaesthetized normal and pancreatectomized dogs has been assessed. Normoglycaemia was achieved in the diabetic dogs with an external artificial B-cell which administered insulin into the peripheral circulation. No differences were found in the levels of blood glucose, glucagon, lactate, pyruvate and plasma non-esterified fatty acids, either in the fasting state or in response to glucose infusion. However, compared to normal animals normoglycaemic diabetic dogs had significantly elevated circulating levels of insulin and alanine at all times. Fasting levels of the same hormones and metabolites were also measured in conscious dogs. Blood pyruvate levels were higher, and plasma non-esterified fatty acid levels lower, in the anaesthetized animals. There were also minor but consistent changes in blood glucose and plasma insulin while glucagon, lactate and alanine levels were unaffected by anaesthesia. In conclusion, controlled barbiturate anaesthesia has relatively minor effects on the metabolic and hormonal status of the dog. The metabolic and hormonal response to glucose infusion in pancreatectomized dogs treated with an artificial B-cell was almost entirely normalized, except for peripheral hyperinsulinaemia and hyperalaninaemia.

Animals↗

Insulin, glucagon, and amino acids during glycemic control by the artificial pancreas in diabetic man.

The artificial endocrine pancreas (AEP) can normalize glycemia at rest and with meals. To determine whether insulin, glucagon, and amino acid profiles are also normalized, nine diabetics on subcutaneous insulin (S/C) and AEP control were compared to ten normal controls (NC). Glycemia was monitored continuously over 10 hr during which meals were consumed. Insulin infusion rate, and the levels of immunoreactive insulin (IRI) (in NC), free insulin (in S/C and AEP), C-peptide, glucagon, and amino acids are reported. Glycemia in AEP started at somewhat higher levels than in NC, but with breakfast and thereafter, it was identical. In S/C, hyperglycemia prevailed throughout, with no systematic change in free IRI. In AEP, both basal and peak free insulin levels, measured in four patients, were significantly higher than in NC. C-peptide values were significantly lower in diabetics and did not change with meals. Basal glucagon values were not different in the three groups and changes with meals were of small magnitude. Branched chain amino acids were higher in S/C and did not increase as in NC. In AEP, levels were lower than NC after the first two meals. Similarly, lysine and threonine were lower in AEP than in NC at the same times. Alanine, though similar at the onset, was lower 2 hr postbreakfast and higher 2 hrs postsupper in AEP and S/C compared to NC. These studies demonstrate that glycemic control with AEP is accompanied by hyperinsulinemia, which could account for the amino acid responses and the small alterations in immunoreactive glucagon (IRG) patterns. Further refinement is needed to obtain full normalization of metabolic profiles.

Adolescent↗

Regression of pituitary tumors, a possible effect of bromergocryptine.

With the advent of the prolactin radioimmunoassay and more sensitive methods of roentgenologic examination, prolactin-secreting pituitary tumors are now being diagnosed with much greater frequency. Definitive treatment has been considered to involve transphenoidal hypophysectomy. The symptoms of hyperprolactinemia including amenorrhea, galactorrhea and infertility can usually be controlled without difficulty by bromergocryptine therapy, but little is known regarding continued tumor growth. Bromergocryptine and other ergot alkaloids have been shown to decrease the production of prolactin and to inhibit the rate of pituitary tumor growth in animal studies. In man, evidence for a similar effect is not as clear. The present study demonstrates tumor regression associated with bromergocryptine therapy in two patients.

Adult↗

Multiple symmetric lipomatosis (Launois-Bensaude syndrome) - adipose tissue insensitivity to cyclic AMP.

Adipocytes prepared from lipomatous tissue of a patient with multiple symmetric lipomatosis have been incubated in the presence of norepinephrine, or insulin, or both. No lipolytic response to norepinephrine could be detected. However, the cellular content of cyclic AMP doubled in response to norepinephrine. Insulin reversed this. The data suggest that fat mobilization from the lipoma is impaired, and that this is due to resistance to the effect of cyclic AMP on hormone sensitive lipase.

Adipose Tissue↗

Effect of calcium on [125I]insulin binding to rat adipocytes.

The specific binding of [125I]insulin to rat adipocytes was reduced in the absence of extracellular calcium. The addition of calcium to the calcium-free medium during incubation restored [125I]insulin binding towards normal. The specific binding of insulin was significantly increased with calcium concentrations as low as 0.5 mM and maximal binding occurred with 5 mM calcium. Scatchard analysis of the data suggests two major binding sites, one a high-affinity low-capacity site (Kd, 1.5 X 10(10) M-1) and the other a lower-affinity high-capacity site (Kd, 4.7 X 10(9) M-1). There was a 50% decrease in the number of high-affinity sites in absence of extracellular calcium. The dissociation curve of receptor-bound insulin was nonlinear both in the absence and presence of extracellular calcium suggesting receptor heterogeneity. The dissociation rate of receptor-bound insulin was greater when insulin was bound in the absence of extracellular calcium than in its presence. These results indicate that extracellular calcium, by increasing the number of high-affinity receptor sites, can alter the the ratio of high-affinity to low-affinity receptors for insulin in adipocytes.

Adipose Tissue↗

The metabolic response to moderate exercise in diabetic man receiving intravenous and subcutaneous insulin.

The responses to moderate exercise of circulating energy fuels and endocrine pancreatic hormones were examined in insulin-dependent diabetics receiving insulin either sc or by continuous iv infusion. Eight subjects received one-third of their usual daily insulin doses sc in the thigh 1 h prior to exercise. Seven subjects exercised during infusion (iv) of insulin at 8-20 mU"min, started 12-14 h earlier. Exercise was on a bicycle ergometer for 45 min at 50% maximum oxygen consumption. The diabetics receiving sc insulin showed a sharp decline in glycemia from elevated resting levels (227 +/- 16 mg/dl), in contrast to the control subjects whose glycemia did not change. The control subjects insulin (IRI) fell, and glucagon (IRG) remained unchanged. In the sc-insulin diabetics, exercise induced a further rise in IRG from elevated levels (296 +/- 76 pg/ml). Resting lactate, pyruvate and alanine were normal and increased as in controls. Though FFA, glycerol and ketone body levels were normal at rest, FFA failed to rise with exercise as in the controls and glycerol and ketone body increments were smaller. RQ increased and remained elevated in contrast to the later fall in controls during exercise. These results are consistent with selective insulin deficiency at rest, and increased insulin effect during exercise. This resulted in greater carbohydrate utilization during exercise, but without the normal shift back toward utilization of fat-derived fuels with continuation of exercise. Diabetics receiving insulin by infusion showed no glycemic change with exercise. Exercise caused greater increases in lactate and pyruvate levels (4-fold), although alanine levels increased only during recovery. The significantly elevated resting FFA levels showed a rise which was sustained at higher than control values during recovery; glycerol and ketone body increments also tended to be greater than in controls. Intravenous insulin sustained euglycemia in exercise, obviating the fall in glycemia with sc insulin. The responses of other metabolite levels were abnormal, and consistent with a subtle degree of underinsulinization.

Adult↗

Normalization of glycemia in diabetics during meals with insulin and glucagon delivery by the artificial pancreas.

An extracorporeal "closed-loop" system has been employed to maintain glycemia in the normal range during consumption of meals in nine insulin-treated diabetics. This artificial pancreas system incorporated continuous blood glucose monitoring (0.05 ml. per minute, delay time 90 seconds), a computer programed to respond to glycemia, and a hormone delivery system. Intravenous insulin delivery rates were determined by control parameters responsive to both glucose concentration and its rate of change. Because insulin-dependent diabetics often defend themselves poorly against hypoglycemia (in some cases due to inadequate glucagon responses), the instrument was also programed for exogenous glucagon delivery. A priori selection of ideal parameters for insulin and glucagon delivery for each individual is not yet possible. Consequently, when the parameters were used for the first time on each subject, they were varied over a reasonable range. This approach resulted in a corresponding variety of glycemic responses, the average of which characterized a set of initial parameters that is generally applicable. Appropriate control parameters are presented that successfully prevented hypoglycemia. Glucagon delivery directly related to glycemia appeared sufficient for this purpose, thus obviating the need for dextrose administration. This system provides a technique for complete normalization of blood glucose concentration in the types of diabetics tested, during both fed and interprandial periods. It has yielded insights essential to the development of more sophisticated future devices.

Adult↗

Exercise and diabetic control.

Exercise, an important component of good diabetic control, is often associated with hypoglycemia in insulin-treated patients. Understanding the mechanism of exercise-induced hypoglycemia and its relationship to the insulin injection site will be helpful in the management of diabetes.

Adult↗