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Biomedical subjects

J W Ensinck

Publications and source records attributed to J W Ensinck.

At least 73 records · Page 4Linked to original sources
PubMed1976

Glucagon response to hypoglycemia in sympathectomized man.

Hypoglycemia stimulates immunoreactive glucagon (IRG) secretion and increases the activity of the sympathetic nervous system. To ascertain if the augmented alpha cell activity evoked by glucopenia is mediated by the adrenergic nervous system, the glucagon response to insulin-induced hypoglycemia of five subjects with neurologically complete cervical transections resulting from trauma, thereby disrupting their hypothalamic sympathetic outflow, was compared to six healthy volunteers. In addition to clinical neurological evaluation, completeness of sympathectomy was verified by failure to raise plasma norepinephrine levels during hypoglycemia compared to the two- and threefold increase observed in controls. Total IRG response (IRG area above basal 0-90 min) and peak IRG levels achieved were the same in the quadriplegics and the controls. Although the glucagon rise tended to be slower, and the peak levels attained occurred later in the quadriplegic patients than in the controls, this response was appropriate for their sugar decline, which was slower and reached the nadir later than in the control subjects. These observations that the glucagon release during insulin-induced hypoglycemia is normal in subjects whose hypothalamic sympathetic outflow has been interrupted provide strong evidence that the sympathetic nervous system does not mediate the glucagon response to hypoglycemia.

Adult↗
PubMed1976

Arginine-stimulated acute phase of insulin and glucagon secretion in diabetic subjects.

To determine if both phases of glucagon secretion are excessive in diabetes, arginine was admimistered intravenously as pulses and as infusions to normal subjects, insulin-dependent diabetics, and noninsulin-requiring diabetics. The acute phase of glucagon secretion, in response to arginine pulses at four different doses (submaximal to maximal alpha-cell stimulating), was indistinguishable in terms of timing, peak levels attained, and total increments comparing controls and diabetics. During the first half of the arginine infusion (500 mg/kg over 30 min) the glucagon rise in controls and diabetics was similar (P greater than 0.1), whereas during the last half of the infusion excessive glucagon levels were seen in the diabetics. No difference in the glucagon responses to arginine administered as either a pulse or an infusion was observed between the two types of diabetics. The acute phase responses of insulin to intravenous, maximal stimulating doses of glucose (20 g) and arginine (2.5 g) were measured in five insulin-independent diabetics. Although the acute insulin response to arginine was normal, there was marked attentuation of the early beta-cell response upon stimulation by glucose. From these results we conclude that although in diabetes excessive glucagon levels are observed with chronic arginine stimulation, the acute phase of glucagon secretion in response to arginine is normal. In addition, the beta-cell in noninsulin-requiring diabetics, although acutely hyporesponsive to glucose, remains normally responsive to another stimulus, arginine.

Adolescent↗
PubMed1976

Somatostatin inhibition of insulin and glucagon secretion in rat islet culture: reversal by ionophore A23187.

Both insulin and glucagon release by monolayer cell cultures of newborn rat pancreas were increased when calcium concentration was raised from 1.8 mEq/1 to 7.2 mEq/1. In low calcium medium, the calcium ionophore A23187 (10 mug/ml) enhanced insulin and glucagon secretion. Incubation with somatostatin (1.0 mug/ml), which inhibited hormonal release in a low calcium environment, paradoxically caused augmented insulin and glucagon secretion when A23187 was also present.

Animals↗
PubMed1976

Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests.

Insulin secretion and glucose disappearance rate were measured in 66 subjects with a wide range of fasting plasma glucose levels. The acute insulin response was present in subjects with fasting glucose levels below 115 mg/dl but was absent above this level. The glucose disappearance rate related to the relative acute insulin response in subjects with fasting glucose below 115 mg/dl and to total insulin response when fasting glucose levels were above 115 mg/dl. A calculated glucose disappearance rate of 1.06 per cent per minute was found when the acute isulin response was zero. All subjects with fasting glucose levels greater than 115 mg/dl had glucose disappearance rates greater than 1.06. These studies support 1) epidemiological data indicating 115 mg/dl as an upper limit of normal for fasting plasma glucose levels and 1.0 per cent per minute as a lower limit of normal for the glucose disappearance rate, and 2) evidence for an important role for the acute insulin response in the determination of glucose disappearance rates during intravenous glucose tolerance tests.

Blood Glucose↗
PubMed1976

Stimulation of glucagon secretion by scorpion toxin in the perfused rat pancreas.

Toxin from the scorpion Leiurus quinquestriatus was used to release norepinephrine from sympathetic nerve endings in the perfused rat pancrease. Addition of toxin, 10 mug./ml., to perfusate containing 0.3 mg./ml. glucose caused a large increase in release of norepinephrine and glucagon. Glucagon secretion was suppressed by perfusate containing 3.0 mg./ml. glucose but still responded to stimulation with scorpion toxin. Atropine, 10 muM, had no effect on either norepinephrine or glucagon release in response to scorpion toxin. The release of glucagon was blocked by 100 muM propranolol, 10 muM phentolamine, or 30 muM phenoxybenzamine. Somatostatin, 55nM, did not affect the release of norepinephrine by scorpion toxin but totally inhibited the glucagon response. These results suggest that pharmacologic stimulation of the adrenergic nerve endings in the rat pancreas can elicit a rapid release of glucagon. This response can be prevented by appropriate concentrations of either alpha or beta adrenergic blocking agents or somatostatin.

Animals↗
PubMed1975

Adaptation to fasting in baboon. II. Regulation of lipolysis early and late in fasting.

Regulation of lipolysis by the sympathetic nervous system, basal insulin, and glucagon was studied in fasted baboons. Beta-Adrenergic mechanisms were evaluated by blockade with propranolol after 24, 40, and 65 h of fasting. Inhibition of lipolysis decreased with increasing duration of fasting. Insulin concentrations were markedly reduced by propranolol at all stages of fasting, whereas glucose and glucagon concentrations were unchanged. The roles of insulin and glucagon were evaluated by a 2-h infusion of somatostatin after 18 and 65 h of fasting. At both times, insulin and glucagon concentrations were markedly reduced. At 18 h of fasting but not at 65 h, lipolysis doubled. At both times the plasma glucose concentration fell 15-30%. At 18 h, preventing the decrease in glucose with glucose infusion prevented the increase in lipolysis. These data suggest that a beta-adrenergic mechanism is largely responsible for regulation of lipolysis early in fasting and that insulin, glucagon, and beta-adrenergic mechanisms play no major part in the maintenance of the accelerated lipolysis later in fasting.

Animals↗
PubMed1975

Inhibition of glucagon and insulin secretion by somatostatin in the rat pancreas perfused in situ.

Perfusion of growth hormone inhibitory factor (somatostatin) into rat pancreas inhibited secretion of glucagon and insulin into medium containing 5.5 mM glucose. A 15-min infusion of arginine (20 mM) greatly increased glucagon and insulin secretion. When perfused simultaneously with arginine, somatostatin (55 nM) abolished the increase in glucagon secretion. The acute phase of insulin secretion in response to arginine was attenuated by somatostatin, and subsequent secretion was decreased to control levels. Pretreatment for 5 min with somatostatin blocked even acute-phase insulin secretion in response to arginine. Somatostatin did not affect basal or glucose-stimulated secretion of insulin from rat pancreatic islets isolated by the collagenase technique. Arginine-stimulated secretion of insulin was enhanced by somatostatin in isolated islets. These results demonstrate a direct effect of somatostatin on the pancreas to inhibit secretion of glucagon and insulin. The failure of somatostatin to inhibit insulin secretion in pancreatic islets may be due to alterations in the beta cells produced by the isolation procedure. It is also possible that the effect of somatostatin on insulin secretion may be mediated indirectly.

Animals↗
PubMed1975

Acute-phase insulin secretion and glucose tolerance in young and aged normal men and diabetic patients.

A defect in the early phase of insulin secretion has been proposed as a major determinant of the impaired glucose homeostasis of adult onset diabetes. Since the process of aging is also associated with a deterioration of glucose tolerance, we have measured the acute phase of insulin secretion and glucose disposal rate (KG) after a 20 g glucose pulse in 11 normal, healthy men greater than 65 yr and compared it with the response in 11 nondiabetic men 20-31 yr. The mean fasting plasma sugar levels of the aged subjects (107 mg/dl), tended to be higher than that of the young (94 mg/dl). Comparison of Kg provided clear separation (P less than 0.01) of the old (mean Kg = 0.93) from the young population (mean Kg = 1.95). The acute insulin response to the glucose pulse when expressed either as the area above basal for the 10 min post stimulation or as the mean encremental increase above basal at 3, 4 and 5 min (delta 3-5 IRI) was the same in both timing and magnitude for the old and young subjects. Although our aged subjects had clearly abnormal kg's their acute phase of insulin secretion in response to glucose was normal. Seven noninsulin requiring diabetics with fasting plasma glucose levels greater than 140 mg/dl similarly studied had abnormal kg's (mean = 0.55) but markedly attenuated early release of insulin. Therefore, even though in the diabetics a deficiency of acute phase insulin secretion may have contributed to their impaired kg, in our aged subjects the lack of correlation between kg and a deficiency of acute phase insulin release suggests that factors other than an impairment in the early phase of insulin secretion are responsible for their glucose intolerance or, that there is a dissociation between the biologic and immunologic activity of insulin in these aged subjects.

Adult↗
PubMed1975

Stimulation of glucagon secretion by ethanol-induced hypoglycemia in man.

In fasted man, ethanol lowers plasma glucose by inhibiting gluconeogenesis with concomitant suppression of insulin release. Since glucose regulation of glucagon (IRG) secretion may be insulin dependent, we have evaluated IRG secretion in this setting of hypoglycemia and insulin deficiency. Mean IRG levels in six men fasted for fifty-six hours rose gradually from a basal level of 57 pg/ml. to 101 pg/ml. During the subsequent four-hour ethanol infusion, mean glucose concentration fell only 18 mg. per 100 ml. (26 per cent of pre-infusion values) yet IRG tripled to 265 pg/ml. Insulin (IRI) fell to unmeasurably low values. Alcohol given after only eight hours of fasting has no effect on plasma levels of glucose, IRG and IRI. These results suggest that the small decrease in extracellular glucose combined with relative insulin deficiency may cause inordinate intra-alpha cell glucopenia and result in exaggerated glucagon release.

Adult↗
PubMed1975

Arginine-stimulated acute phase of insulin and glucagon secretion. I. in normal man.

To document and characterize the immediate phase of glucogen secretion as detected in peripheral blood in man, we have given pulses of L-arginine (0.1 gm. to 10.0 gm.) intravenously over twenty to thirty seconds to twenty-three healthy young men. Peak glucagon and insulin levels averaging four and five times basal levels respectively were reached two to five minutes after arginine administration and had returned to baseline levels by fifteen to thirty minutes. Computing the area above basal for the initial ten minutes after arginine stimulation established a dose-response relationship for the acute phases of glucagon and insulin secretion. A maximal glucagon response was elicited by doses of arginine of 5.0 gm. or greater, whereas for insulin, the plateau was reached at 2.5 gm. of arginine. Sequential 5.0-gm. pulses of arginine administered every thirty minutes showed that there was no augmentation or attenuation of the timing, magnitude (area 0-10 minutes) or absolute peak values reached for either the glucogon or insulin responses. The effect of induced hyperglycemia on the acute phase of insulin and glucagon secretion was assessed by administering the arginine during marked elevation of ambient glucose concentration achieved by the intravenous administration of glucose. This resulted in marked suppression of the acute glucagon response and dramatic accentuation of the insulin response.

Adolescent↗
PubMed1975

Are research subjects really informed?

To determine how adequately patients who participate as subjects for clinical investigation understand their commitment, 50 patients admitted to the Clinical Research Center of the University of Washington were interviewed. Their responses were compared with the detailed statements in the consent forms for the 23 specific protocols under which they were being studied. In spite of careful controls in accord with guidelines of a review committee, only half the patients were able to describe accurately their expectations of the studies to which they had given signed consent.

Adolescent↗
PubMed1975

Central factors in the control of insulin and glucagon secretion.

A complete system for neural regulation of insulin and glucagon secretion from the ventral hypothalamus to the autonomic cholinergic and adrenergic nerves of the endocrine pancreas is described. Both physiologic and pathophysiologic states of altered metabolism can be partly explained by activation of this neural system. Direct hypothalamic humoral control of the endocrine pancreas has been evaluated by studies of the hypothalamic hormone somatostatin, or somatotrophin release inhibiting factor (SRIF). Somatostatin has been shown to inhibit pancreatic glucagon and insulin secretion when infused into the pancreatic artery of intact dogs in vivo in the absence of a change of systemic glucose concentration. Although less inhibition is observed when the same amount of hormone is infused intraportally, the potency of somatostatin when given directly into the liver suggests extrapancreatic effects as well as direct pancreatic effects on insulin and glucagon secretion.

Animals↗
PubMed1974

The effect of adrenergic blockade on the glucagon responses to starvation and hypoglycemia in man.

In an attempt to ascertain whether the sympathetic nervous system modulates glucagon release in man during starvation and hypoglycemia, the influence of alpha and beta adrenergic blockade on glucagon responses was studied in young, healthy men subjected to fasting and insulin-induced hypoglycemia. Six volunteers fasted for 84 h on three separate occasions. Plasma immunoreactive glucagon (IRG), measured initially at 12 h, climbed gradually from mean levels of 54 pg/ml to a zenith of 124 pg/ml at 48 h, with maintenance of these levels for the duration of the fast. The infusion of propranolol or phentolamine throughout the terminal 24 h of the second and third fasts failed to alter the pattern of IRG release. After an overnight fast, five volunteers received insulin intravenously, which evoked a mean rise in plasma IRG levels from 63 pg/ml to a maximum of 256 pg/ml at 30 min. The concurrent administration of propranolol or phentolamine did not modify the glucagon responses to insulin-induced hypoglycemia. These data suggest that the augmented glucagon release in man during starvation or after hypoglycemia is not significantly regulated by signals from the adrenergic nervous system.

Adolescent↗