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Biomedical subjects

N Freinkel

Publications and source records attributed to N Freinkel.

At least 91 records · Page 5Linked to original sources
PubMed1976

Drug modification of hypothermia induced by CNS glucopenia in the mouse.

2-Deoxy-D-glucose (2-DG), insulin, or norepinephrine (NE), when injected into the cerebral ventricles of conscious mice, produce decreased rates of O2 consumption and hypothermia. These changes are accompanied by hyperglycemia with 2-DG, hypoglycemia with insulin, and normoglycemia with NE. Desipramine blocks the reduction in body temperature and O2 consumption produced by each of these agents, but does not modify significantly their effects on plasma glucose. The latter suggests that the thermal and oxidative responses to central glucopenia can be dissociated from concurrent alterations in circulating glucose. Propranolol enhances the hypothermic response produced by administered 2-DG, insulin, or NE. Phentolamine, however, antagonizes the hypothermia only with NE, indicating the 2-DG and insulin are probably not acting through the release of endogenous NE.

Animals↗
PubMed1976

Epidemiologic findings on the relationship of time of day and time since last meal to glucose tolerance.

Data from 10,559 men and women, age 30-64, participating in the morning and afternoon in a Chicago Health Department multiphasic screening project, were used to determine the effects of time of day and time since last meal on the values for plasma glucose one and two hours following oral challenge with 100 gm. of glucose. Mean plasma glucose values and rates of suspect glucose intolerance (based on several cutpoints) were sizeably higher in the afternoon than in the morning. In addition, plasma glucose values increased with time elapsed since the last meal, up to 10 hours postprandially. Thereafter, both one- and two-hour plasma glucose values tended to exhibit a decline. Analysis of covariance confirmed that fluctuations in glucose tolerance were related to time of day and time since last meal, but the effects of each parameter were exerted independently.

Adult↗
PubMed1975

Inter-relations between the phospholipids of rat pancreatic islets during glucose stimulation, and their response to medium inositol and tetracaine.

1. Isolated rat pancreatic islets subjected to an increase in glucose concentration from 0.5 to 3 mg/ml showed an increased insulin secretion and 32P-labelling of their phospholipids, especially of phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, and CDP diglyceride. Neither fructose or inositol produced a similar effect. 2. The enhanced labelling of CDP diglyceride and phosphatidylglycerol was suppressed by adding inositol (0.1 mg/ml), while the phosphatidylinositol labelling was increased still further. 3. Tetracaine (0.5 mM), an antagonist of insulin secretion, inhi-ited phosphatidylinositol synthesis while phosphatidylglycerol, CDP diglyceride and phosphatidic acid formation were markedly increased. These effects on phospholipid synthesis were substantially reversed by adding inositol to the medium. Tetracaine also prevented the catabolism of phosphatidylinositol in prelabelled islets but this inhibiton was not reversed by inositol. 4. Inositol addition did not affect insulin secretion in glucose-stimulated islets nor secretion in tetracaine-treated islets. This need not exclude a possible role for heightened phosphatidylinositol cleavage in stimulated insulin secretion.

Animals↗
PubMed1975

Carbohydrate metabolism in pregnancy: XIII. Relationships between plasma insulin and proinsulin during late pregnancy in normal and diabetic subjects.

To assess the effects of pregnancy on the relationships between plasma insulin and proinsulin, studies were performed during late gestation in women with normal carbohydrate metabolism or diabetes mellitus. Plasma was secured after overnight fast and 1, 2, and 3 hours following oral glucose (100 g). Samples were analyzed directly for total immunoreactive insulin (TIR) and for insulin and proinsulin following plasma fractionation by gel filtration. Fractionation disclosed that most of the normal gestational increase in basal and glucose-stimulated TIR can be ascribed to insulin rather than disproportionate increments in proinsulin-like components. Normal proinsulin/insulin relationships were also preserved in mild diabetics despite greater variability in their TIR response to glucose. Thus, mild carbohydrate intolerance during pregnancy is not attended by abnormalities in plasma proinsulin. In contrast basal proinsulin levels were elevated in 4 of 9 pregnant subjects with diabetes sufficiently severe to necessitate subsequent insulin therapy. Following glucose administration in the severe diabetics, the relative contribution from proinsulin to TIR was altered so that ratios of circulating proinsulin/insulin were increased at all levels of blood sugar. Postpartum tests of glucose tolerance in some of the normal and mildly diabetic subjects confirmed that pregnancy per se does not modify appreciably the relationships between plasma insulin and proinsulin although there may be some tendency for proinsulin to account for a smaller proportion of TIR.

Blood Glucose↗
PubMed1975

Plasma C-peptide and diagnosis of factitious hyperinsulinism. Study of an insulin-dependent diabetic patient with "spontaneous" hypoglycemia.

Factitious hyperinsulinism was suspected in a patient with an 11-year history of insulin-dependent, ketosis-prone diabetes mellitus who began to experience repetitive episodes of "spontaneous" hypoglycemia. Insulin mediation of the hypoglycemia was confirmed by documenting that urinary insulin and total extractable insulin in plasma increased during periods of hypoglycemia. Failure to detect significant amounts of human C-peptide by radioimmunoassay during periods of hypoglycemia or in response to stimulation with glucagon, leucine, or tolbutamide indicated that the insulin was not endogenous. The diagnosis of factitious hyperinsulinism was ultimately proved by the finding of radioactivity in the patient's urine after 131-I Hippuran was added to a vial of insulin found in the patient's room.

Diabetes Mellitus↗
PubMed1974

Rapid transient efflux of phosphate ions from pancreatic islets as an early action of insulin secretagogues.

Anionic fluxes during the membrane realignments of stimulated insulin release have not been characterized previously although cations have been implicated in stimulus-secretion coupling. We have shown that a limited packet pulse of phosphate release ("phosphate flush") begins at the same time that the first phase of insulin secretion may occur. To demonstrate this phenomenon, we have prelabeled islets, obtained from rat pancreas by collagenase digestions, by incubation with [(32)P]orthophosphate. When such prelabeled islets are perifused with Krebs-Ringer bicarbonate containing 0.5 mg/ml D-glucose, a basal rate of efflux of radioactivity is established; transfer to perifusates containing 3.0 mg/ml D-glucose elicits an increased (32)P efflux within 1-2 min to peak values which are 7- to 21-fold greater than basal. The total duration of this "phosphate flush" approximates 10 min and exceeds the duration of the first phase of stimulated insulin secretion. With lesser concentrations of glucose, the flush exhibits dose-response relationships, and with 3 mg/ml glucose, a second flush can be elicited by restoring basal conditions and stimulating anew with 3 mg/ml glucose. The phenomenon is highly specific and can be reduplicated by other secretagogues (L-leucine) or sugars (D-mannose) which are also known to elicit insulin release but not by sugars which fail to affect insulin secretion (D-galactose, D-fructose, i-inositol, L-glucose). The efflux of radioactivity consists entirely of [(32)P]orthophosphate. Phosphate flush persists in phosphate-free media, Ca(++)-free media, and when insulin release is obtunded by adding Ni(++) (2 mM) to the perifusates. Thus, efflux of [(32)P]orthophosphate can be dissociated from insulin extrusion, and from net influx of ionic phosphate or calcium. Membrane stabilization with D(2)O or 1.0 mM tetracaine reversibly inhibits phosphate flush. Although the mechanism by which this effect occurs has not yet been established, the phosphate flush appears to constitute one of the earliest and hitherto unknown indices of the excitatory state in pancreatic islets.

Animals↗