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Biomedical subjects

D Porte

Publications and source records attributed to D Porte.

At least 199 records · Page 11Linked to original sources
PubMed1975

Reversible abnormalities in postheparin lipolytic activity during the late phase of release in diabetes mellitus (postheparin lipolytic activity in diabetes).

To test whether abnormalities in multiphasic release of lipoprotein lipase are associated with hypertriglyceridemia in diabetes mellitus, postheparin lipolytic activity (PHLA) was measured during a high-dose, constant heparin infusion in 20 diabetic subjects with hypertriglyceridemia, 25 nondiabetic hypertriglyceridemic subjects and 7 normal subjects. The standard low heparin dose PHLA and the PHLa during the early phase of the heparin infusion were the same in all groups. In constrast, the PHLA during the late phase of the heparin infusion was lower in the 12 untreated diabetic subjects than in the 25 nondiabetic hypertriglyceridemic and the 7 normal subjects (p less than 0.001). An abnormality in late phase PHLA in the untreated diabetic subjects was more apparent when it was compared to the level of PHLA attained during the early phase of the heparin infusion (Equilibrium PHLA/60 min PHLA). The relative PHLA in the late phase of the infusion was lower in the untreated diabetic subjects (0.671 +/- 0.147) than in the nondiabetic hypertriglyceridemic subjects (0.847 +/- 0.019, p less than 0.001), or in the chronically treated diabetic subjects (0.823 +/- 0.108, p less than 0.05). Among the untreated diabetic subjects, increasing fasting glucose levels were associated with both decreasing absolute PHLA levels at the late phase of the infusion (r = 0.61, p less than 0.02) and greater decreases in relative PHLA during the infusion (r = -0.80, p less than 0.001). Treatment of the diabetes with long-term oral sulfonylurea or insulin therapy corrected the abnormality in the late phase PHLA with an associated decrease in plasma triglyceride levels (p less than 0.001). In five subjects with a deficient PHLA response to a standard, low dose of heparin, the PHLA response was low throughout the heparin infusion. With treatment, the PHLA response to the low heparin dose corrected rapidly toward normal in those two diabetic subjects with PHLa deficiency, and the early PHLA response during the heparin infusion increased. However, the late phase abnormality in all untreated diabetic subjects did not correct to normal until after several months of antihyperglycemic therapy. In the untreated diabetic subjects the degree of elevation of the plasma triglyceride level appeared to result from the interaction of the abnormality in PHLA with the presence or absence of an inherited familial lipid disorder.

Adult↗
PubMed1975

Effect of intracisternal insulin on plasma glucose and insulin in the dog.

The intracisternal administration of insulin (0.2 U./kg.) to anesthetized dogs resulted in an increase of arterial immunoreactive insulin and a decrease of plasma glucose relative to a control injection. The arterial responses were significantly attenuated when the insulin was administered to the cisternum of subdiaphragmatically vagotomized dogs. When cerebrospinal fluid glucose was lowered by injecting pneumococcal neuraminidase intracisternally, no peripheral hyperinsulinemia resulted, indicating that increased spinal fluid insulin and its consequent increase of glucose uptake, rather than decreased spinal fluid glucose, is necessary to elicit the vagally mediated insulin secretion and hypoglycemia. It is hypothesized that increased spinal fluid insulin causes an increased glucose uptake of some glucoregulatory area of the brain and that the elicited reflex is vagally mediated pancreatic insulin secretion.

Animals↗
PubMed1975

Effect of cerebral intraventricular insulin on pancreatic insulin secretion in the dog.

The effect of cerebral intraventricular insulin on pancreatic insulin secretion was investigated. An extracorporeal pancreatic blood circuit was established after laparotomy to monitor blood flow and insulin concentration directly from the superior pancreaticoduodenal vein. Phentolamine was infused throughout (0.2 mg./min. intravenously) to block alpha-adrenergic effects of any catecholamine secretion induced by surgical stress. Glucose (1.5 mg./kg./min. intravenously) was infused to maintain a constant baseline stimulation of insulin secretion. Six dogs received insulin and six control dogs received saline through a spinal needle stereotaxically placed into the left lateral cerebral ventricle. After central injection of insulin (0.2 U./kg.) there was a significant increase of pancreatic output as early as five minutes. It is concluded that the pancreatic beta-cells are under the influence of insulin-sensitive cells of the CNS.

Animals↗
PubMed1975

Effect of force-feeding upon basal insulin levels of rats.

Rats were over- or under-fed to achieve a wide range of body weights. The effect of this treatment on basal insulin levels, with and without pretreatment with atropine, was examined. Basal insulin was positively correlated with body weight and this relationship was essentially unchanged in the presence of atropine.

Animals↗
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

Inhibition of in vivo insulin secretion by prostaglandin E1.

To determine the effect of prostaglandin E(1) (PGE(1)) infusion upon in vivo insulin secretion, serum insulin responses after an intravenous glucose pulse (2 g) were measured before and during an intravenous infusion of PGE(1) (10 mug/min) in 11 anesthetized dogs. Circulating insulin decreased significantly during PGE(1) infusion were significantly less than control responses. Three dogs received PGE(1) infusions into the thoracic aorta to preclude pulmonic and hepatic degradation of PGE(1) before its arrival at the pancreatic artery; inhibition of insulin secretion was again seen. Inhibition of insulin secretion could not be related to the degree of arterial hypotension induced by intravenous PGE(1), and despite alpha adrenergic blockade with intravenous phentolamine, PGE(1)-induced inhibition of glucose-stimulated insulin responses persisted. Significant increments in systemically circulating PGE levels during intravenous PGE(1) infusions were documented by radioimmunoassay. These studies demonstrate that systemic PGE(1) infusion inhibits insulin secretion and that this effect could not be shown to be dependent upon alpha adrenergic activity.

Animals↗
PubMed1973

Neural regulation of insulin secretion in the dog.

The effects of stimulation of the mixed autonomic nerve to the dog pancreas has been studied under conditions in which both pancreaticoduodenal vein blood flow and insulin concentration were determined. Stimulation resulted in increased insulin output, which was blocked by prior administration of atropine. Blood flow was reduced by stimulation in proportion to the rate of stimulation. At 40 stimuli/s a maximum effect was found at 1 min with a gradual return toward base line despite continued application of the stimulus. Atropinization had no effect on blood flow changes. Insulin responses to 0.1 g/kg glucose were reduced on the average 40% by simultaneous stimulation of the pancreatic nerve at 40 cycles/s in atropinized animals. These studies establish this preparation as a reproducible model for the direct examination of autonomic influences on endocrine pancreatic function. From them it is concluded that the nerve supply to the endocrine pancreas of the dog is sufficient to inhibit insulin secretion by activation of the sympathetic nerves and to stimulate insulin secretion by activation of the parasympathetic nerves.

Animals↗
PubMed1973

The glucose receptor. A defective mechanism in diabetes mellitus distinct from the beta adrenergic receptor.

Acute serum insulin responses in 10 normal subjects after rapid intravenous injection of glucose (5 g) or isoproterenol (2 mug) were of similar magnitude and timing (glucose: 431+/-349%; mean Delta3-5' insulin (IRI)+/-SD, per cent basal and isoproterenol: 359+/-216%; mean Delta2-4' IRI+/-SD, per cent basal). To elucidate the relationship of glucose-induced insulin secretion to pancreatic beta adrenergic receptors and the implications of this relationship with regards to abnormal insulin secretion in diabetes mellitus, two questions were studied. (a) To determine whether glucose-induced insulin secretion is dependent upon beta adrenergic activity, the effect of beta adrenergic blockade with intravenous propranolol (0.08 mg/min) upon acute insulin responses to isoproterenol and glucose were compared in normal subjects. (b) To determine whether acute insulin responses to beta adrenergic stimulation were intact in diabetes mellitus, the effect of isoproterenol upon serum insulin levels was studied in diabetic subjects. Beta adrenergic blockade in the normal subjects obliterated acute insulin responses to isoproterenol (before: 361+/-270%, during: - 31+/-15%; n = 6, P < 0.001) but did not significantly affect responses to glucose (before; 311+/-270%; during: 284+/-206%; n = 5). The mean acute insulin response after isoproterenol in the diabetic group was significantly elevated over basal levels (152+/-74%; n = 10, P < 0.001) but the response after glucose was not (- 11+/-11%). These data suggest that insulin responses to glucose in normal subjects are mediated by specific pancreatic glucose receptors which are independent from beta adrenergic receptors and that abnormal glucose-induced insulin secretion in diabetics is due to defects within glucose receptors and not beta adrenergic receptors as has been previously hypothesized.

Blood Glucose↗