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Biomedical subjects

D Porte

Publications and source records attributed to D Porte.

At least 181 records · Page 10Linked to original sources
PubMed1978

Mechanisms of impaired acute insulin release in adult onset diabetes: studies with isoproterenol and secretin.

Previous work has suggested that impaired islet glucose recognition occurs in patients with adult onset diabetes, as acute insulin release is absent after iv glucose but present after beta adrenergic stimulation with isoproterenol (Iso). However, insulin responses to Iso were variably reduced as compared to normal in the diabetics. In order to evaluate the importance of the Iso dose, dose-response studies were performed in 9 diabetics (fasting plasma glucose greater than 150 mg/dl) and 10 age-matched controls. In both control subjects and diabetics, 0.5 microgram Iso produced no insulin response; 2 micrograms Iso produced an intermediate response; and 8 and 12 micrograms Iso produced a higher response. The insulin responses to the larger doses of Iso were lower in diabetics than control subjects (8 micrograms, 20 +/- 5 vs. 39 +/- 6 (P less than 0.025); 12 micrograms, 21 +/- 6 vs. 37 +/- 4 (P less than 0.05); means +/- SEM, microU/ml). Of 16 diabetics who received 12 micrograms Iso, 5 had insulin responses greater than 2 SD below the control mean, while others had responses that spanned the entire range of normal. Seven diabetics also were given iv secretin (150 U). Their insulin responses to secretin correlated with the responses to Iso (r = 0.83, P less than 0.02). Thus, patients with subnormal responses to Iso also had low secretion responses. The abnormalities of acute insulin secretion in diabetics can be explained by a lesion variably affecting islet membrane receptors; some patients may have glucose receptor damage, but intact responses to other stimuli, and others may have more widespread damage affecting beta-adrenergic and secretin responses as well. Alternatively, there may be heterogeneity in adult onset diabetes, as patients with low responses to all stimuli could have a qualitatively different lesion affecting insulin secretory capacity rather than membrane receptors.

Aged↗
PubMed1978

Glycosylated hemoglobin in normal subjects and subjects with maturity-onset diabetes. Evidence for a saturable system in man.

Concentrations of glycosylated hemoglobin (GHb) are elevated in diabetes mellitus and are believed to reflect previous metabolic control. To better define possible determinants of GHb in man, we investigated the relationship between GHb and both fasting plasma glucose (FPG) and basal insulin (IRI) in 42 normal subjects and 29 patients with maturity-onset diabetes. Concentrations of GHb in diabetic subjects (12.7 +/- 3.4, x +/- S.D., per cent total hemoglobin) were significantly higher than in normal subjects (8.2 +/- 1.2, p less than 0.001). In normal subjects, FPG (r = 0.52) and GHb (r = 0.58) (both p less than 0.001) correlated with age. GHb did not correlate with IRI in either group. However, GHb was closely associated with FPG in both normal (r = 0.60, p less than 0.001) and diabetic (r = 0.85, p less than 0.001) subjects. Linear regression analysis of the data for the two groups combined was highly significant (r = 0.91, p less than 0.001). However, the slope of the regression line for GHb versus FPG seen in normal subjects was significantly steeper than that of diabetic patients (p less than 0.005). A curve describing a nonenzymatic saturable model was also found to fit the data of the two groups combined (r = 0.85, p less than 0.001), suggesting the possible existence of a saturable system for glycosylation in man.

Adult↗
PubMed1978

Autonomic epilepsy: clonidine blockade of paroxysmal catecholamine release and flushing.

We studied a 59-year-old man with transient paroxysms of hypertension, tachycardia, and flushing in whom pheochromocytoma was excluded. Although catecholamine excretion was normal, plasma catecholamine levels rose from normal basal levels (282 +/- 14 pg/ml) to increased levels (585 +/- 67 pg/ml; x +/- SEM; n = 4) at the peak of spells. Other hormones or substrates expected to rise with nonspecific "stress" did not increase after paroxysms. Therapy with clonidine (0.2 to 0.4 mg/day) suppressed basal catecholamines to undetectable levels and markedly reduced peak levels during spells (80 pg/ml). An epileptic pathogenesis was suggested by stereotypic olfactory and epigastric prodromata before spells, and abolition of paroxysms with the anticonvulsant carbamazepine. This patient represents a rare case of autonomic epilepsy with the seizure focus in the temporal lobe.

Autonomic Nervous System↗
PubMed1978

Comparison of double- and single-isotope enzymatic derivative methods for measuring catecholamines in human plasma.

We directly compared the reliability of a single-isotope enzymatic derivative technique for measurement of plasma catecholamines with that of the well-established double-isotope method. A significant (p less than 0.001) correlation was observed between measurements (n = 52) in the two assays, both for norepinephrine (r = 0.97) and epinephrine (r = 0.80). Means and coefficients of variation for the two analytes in a pooled specimen of plasma, measured repeatedly during six months, were virtually identical by each assay method. Basal plasma catecholamine concentrations in two different groups of apparently healthy subjects were also similar by each method. Dopamine concentrations in plasma were consistently below the limits measurable by either technique. The single-isotope assay requires half the assay time and 1/200th the sample as the double-isotope method. We conclude that this assay is just as reliable as the double-isotope technique and gives virtually identical values for norepinephrine and epinephrine concentrations in the physiological range.

Adult↗
PubMed1977

Phentolamine prevents the somatostatin-mediated inhibition of pancreatic glucagon secretion.

This study was undertaken to assess the role of alpha-adrenergic receptors in the somatostatin-mediated inhibition of pancreatic glucagon secretion. In dogs, somatostatin inhibited the pancreatico-duodenal vein output of glucagon. During an infusion of the alpha-adrenergic blocking agent phentolamine, somatostatin did not significantly inhibit the output of glucagon. Thus, alpha-adrenergic mechanisms appear to influence the ability of somatostatin to decrease pancreatic glucagon secretion.

Animals↗
PubMed1977

Relationship between plasma and cerebrospinal fluid insulin levels of dogs.

Several experiments are reported in which insulin or glucose was administered intravenously to anesthetized dogs. Plasma and cerebrospinal fluid levels of glucose and immunoreactive insulin were determined at several intervals before and after the administrations. Intravenous insulin (0.2 U/kg) administered as either a pulse or a 1-h infusion caused a large increase of plasma insulin, but a relatively small increase of cerebrospinal fluid insulin. When endogenous insulin was elevated by the administration of glucose (100 mg/kg), cerebrospinal fluid insulin changed only slightly. A significant correlation was found between steady-state plasma and CSF endogenous insulin levels. The results are interpreted to indicate that the level of insulin in the cerebrospinal fluid reflects basal plasma level plus an integral over time of the insulin response to challenge. The implications of such a system are discussed.

Animals↗
PubMed1977

Selective osmoreceptor dysfunction in the syndrome of chronic hypernatremia.

A patient with the syndrome of chronic hypernatremia (serum Na+: mean = 154, range 139-184 mEq/l, n = 30) and hypodipsia due to a hypothalamic injury was studied to evaluate osmolar and baroreceptor control of arginine vasopressin (AVP) secretion. Resting plasma AVP levels measured by radioimmunoassay were inappropriately low for the degree of plasma hyperosmolality: range = less than 0.5-2.1 pg/ml, n = 10, with corresponding levels of plasma osmolality (P osM) greater than 300 m osmol/kg, suggesting either direct damage to the AVP synthesis and storage area or impaired afferent osmoreceptor function. Direct pituitary damage seemed unlikely, since anterior pituitary function was normal by standard testing. The existence of adequate neurohypophyseal stores of AVP was demonstrated by baroreceptor stimulation with the hypotensive agent trimethaphan (Arfonad): plasma AVP rising to 50.0 pg/ml during transient hypotension (BP = 70/0). Osmoreceptor function was evaluated during acute water loading followed by hypertonic saline infusion. During hypertonic saline infusion plasma AVP levels correlated with P osM (R = .87, P less than .01, n = 8), suggesting some residual osmotic regulation of AVP release. The osmotic threshold for AVP release (the x-axis intercept of the plasma AVP-P osM regression line) was not higher than normal. However, the AVP levels throughout this study remained markedly subnormal for the degree of plasma hyperosmolality (maximum plasma AVP = 1.9 PG/ML when P os M = 327 M OSMOL/KG). Since a substantial amount of AVP was released with baroreceptor stimulation, the inadequate rise in plasma AVP level with hyperosmolality indicates that afferent input from the osmoreceptor/thirst area of the hypothalamus is selectively impaired in this patient. These findings directly demonstrate a dissociation of osmoreceptor function from the AVP secretory apparatus in man.

Arginine Vasopressin↗
PubMed1976

A role for alpha-adrenergic receptors in abnormal insulin secretion in diabetes mellitus.

To determine whether endogenous alpha-adrenergic activity contributes to abnormal insulin secretion in nonketotic, hyperglycemic, diabetic patients, alpha-adrenergic blockade was produced in normal and diabetic subjects. The diabetics had a significantly (P less than 0.01) greater increase in circulating insulin 1 h after an intravenous phentolamine infusion than did the normal subjects. During the phentolamine infusion, there was also a significant augmentation of acute insulin responses to intravenous glucose (20 g) pulses in normal subjects (P less than 0.05) and diabetics (P less than 0.02); this augmentation was fivefold greater in the diabetics. Simultaneous treatment with the beta-adrenergic blocking agent, propranolol, did not alter these findings. Thus a role for exaggerated endogenous alpha-adrenergic activity in abnormal insulin secretion of the diabetic subjects is suggested. To determine whether this alpha-adrenergic activity might be related to elevated circulating catecholamines, total plasma-catecholamine levels were compared in normal and nonketotic diabetic subjects given intravenous glucose pulses. These levels were significantly greater (P less than 0.02) in the diabetic compared to the normal group before the glucose pulse, and increased significantly in both groups (P less than 0.02 and less than 0.001, respectively) after the pulse. These data suggest that excessive catecholamine secretion may lead to an abnormal degree of endogenous alpha-adrenergic activity, which contributes to defective insulin secretion in diabetic subjects.

Autonomic Agents↗
PubMed1976

Beta adrenergic receptor dysfunction in hypoxic inhibition of insulin release.

Insulin secretory responses were measured in air-breathing puppies given epinephrine, and compared with insulin responses during acute hypoxia. In puppies with oxygen deficiency, insulin levels declined, whereas during epinephrine infusion, they remained stable or increased slightly. When glucose was given during phentolamine administration, insulin levels rose more in the epinephrine-treated animals than in the hypoxic animals, despite similar blood glucose levels. Theophylline-induced insulin release was increased by epinephrine, but inhibited by hypoxia. When the beta adrenergic blocking agent, propranolol, was given with the epinephrine, the insulin response to theophylline was markedly reduced and similar to that observed during hypoxia. Control studies with propranolol showed no effect of this agent on glucose-induced insulin release. Isoproterenol infusion caused elevated insulin levels during air ventilation but this response was suppressed by hypoxia. From these data, we have concluded that the difference between hypoxia and epinephrine can be explained by a reduced ability of catecholamines to stimulate the beta adrenergic receptor during hypoxia. We hypothesize that this effect leads to an unmodulated alpha adrenergic inhibition of insulin release.

Animals↗
PubMed1976

Phentolamine blocks the somatostatin-mediated inhibition of insulin secretion.

This study was undertaken to determine the influence of alpha-adrenergic blockade upon the somatostatin-mediated inhibition of insulin secretion. Somatostatin inhibited both the basal and glucose-stimulated pancreaticoduodenal vein insulin output of dogs. This effect was not observed during a simultaneous infusion of phentolamine, an alpha-adrenergic blocker. It is proposed that alpha-adrenergic mechanisms play a role in the inhibition of insulin secretion by somatostatin.

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

The effect of rate and dose of glucose infusion on the acute insulin response in man.

Two types of studies have been done to determine the importance of the rate of plasma glucose concentration change to the magnitude of the acute insulin response following an intravenous glucose injection in normal men. When an identical amount of glucose (20 g) was given at varying infusion rates (1.67 g/min to 66.7 g/min), the magnitude of the acute insulin response was found to be proportional to the rate. When various doses (5 g to 20 g) were given at the identical rate (1.67 g/min) the acute insulin response did not change. When 5 g of glucose was given in 0.3 and 3 minutes, a sub-maximal acute insulin response resulted which was still rate-dependent (delta peak IRI=35.5 +/- 5 at 5 g/0.3 minutes, 21.8 +/- 3 at 5 g/3 minutes). We have concluded that the human islet acts as a sensor for both the concentration of plasma glucose and the rate of change in plasma glucose. Islet perception of both these phenomena are critical factors in the determination of the magnitude of the acute insulin response.

Adult↗