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Biomedical subjects

R L Lavine

Publications and source records attributed to R L Lavine.

At least 19 recordsLinked to original sources
PubMed1986

Virilizing Leydig cell adenoma of adrenal gland.

We describe the third report testosterone-producing, virilizing, adrenal Leydig cell adenoma, which was identified in a oophorectomized postmenopausal female patient. Light- and electron-microscopy demonstrated typical Leydig cell differentiation, including numerous intracytoplasmic and intranuclear Reinke crystals and rice-like bodies (elementary tubular inclusions). Testosterone production by the adenoma was demonstrated by the immunoperoxidase technique. We propose that adrenal Leydig cell adenomas arise as a result of ovarian gonadal stromal metaplasia associated with elevated follicle-stimulating hormone and luteinizing hormone in the postmenopausal female patient. Adrenal Leydig cell lesions must be considered in the virilized woman with elevated testosterone levels and normal levels of the adrenal androgens and their 17-ketosteroid metabolites.

Adenoma↗
PubMed1984

L-Asparaginase diabetes mellitus in rabbits: differing effects of two different schedules of L-asparaginase administration.

The diabetogenic effect of daily injections of 1000 i.u./kg body wt. E coli L-asparaginase was studied in male New Zealand white rabbits and compared with the diabetogenic effect of a single bolus of 10,000 I.U. E coli L-asparaginase/kg body wt. to determine whether the schedule of administration of the drug altered the diabetic syndrome produced. A daily injection of 1000 i.u. L-asparaginase/kg. body wt. was continued for 30 days. During this time glucose levels in rabbits allowed free access to food rose steadily, reaching levels of 717 +/- 63 mg/dl the day after the last injection. Levels of immunoreactive insulin fell, reaching their nadir, 53 +/- 4 pg/ml (approximately 50% of baseline) at 25 days. Glucose levels declined when therapy was discontinued, but remained significantly above control levels 46 days after insulin injections were stopped. (Glucose levels in L-asparaginase-treated groups vs. those in controls on day 46 after discontinuation: 116 +/- 3 vs. 104 +/- 1 mg/dl; P less than 0.0025.) Levels of immunoreactive insulin rose when therapy ended, reaching control levels 17 days after discontinuation. In contrast, a single bolus injection of 10,000 I.U. L-asparaginase/kg resulted in hyperglycemia with hyperinsulinemia. These data suggest that L-asparaginase can induce either a hypoinsulinemic or a hyperinsulinemic diabetic syndrome depending on the schedule of administration of the L-asparaginase and that a mild abnormality in glucose homeostasis persists after discontinuation of L-asparaginase therapy.

Animals↗
PubMed1982

E. coli L-asparaginase and insulin release in vitro.

Glucose induced insulin release, from collagenase isolated islets of Langerhans obtained from non diabetic male New Zealand White rabbits, was inhibited in vitro by E. coli L-asparatinase. This inhibition was time and dose dependent with maximal inhibition being attained after 1 1/2 hr incubation using a dose of 1000 I.U. L-asparaginase/ml. Tolbutamide potentiated glucose-induced insulin release in the presence of inhibitory doses of the L-asparaginase. This potentiation was decreased at higher dose levels of L-asparaginase. L-leucine, L-arginine and theophylline also potentiated glucose-induced insulin release in the presence of L-asparaginase. This potentiation was intact in the presence of all doses of L-asparaginase tested. Glucose induced insulin release, from collagense isolated islets obtained from male New Zealand White rabbits rendered hypoinsulinemic and diabetic by daily intravenous injections of L-asparaginase in vivo, was similar to that of islets of non diabetic control rabbits when the islets were incubated in vitro in te absence of L-asparaginase. These data suggest that the hypoinsulinemic diabetic syndrome produced by the anti-tumor enzyme, L-asparaginase, is produced at least in part by the suppression of insulin release and that this suppression requires the enzyme to be present.

Animals↗
PubMed1981

Mesocricetus auratus: a new animal model for studying diabetes mellitus in pregnancy.

To document the feasibility of using Syrian hamsters to study diabetic pregnancies, mature virgin hamsters (Mesocricetus auratus) were given a single injection of streptozotocin, inseminated the third succeeding ovulation following the injection, and the fetuses examined 1 day prior to delivery (Day 15 post-conception). A dose-response to streptozotocin was observed with an optimum dose of 56 mg/kg body weight. A significantly elevated serum glucose (459 +/- 34 mg/dl versus 160 +/- 15 mg/dl; p less than 0.01) was observed concomitantly with a decrease in maternal weight change 4.89 +/- 9.2 versus 32.5 +/- 5.8 g; p less than 0.05). Fetuses from treated dams were significantly smaller (24.3 +/- 0.9 mm versus 27.4 +/- 0.9 mm; p less than 0.05) and lighter, and 47% of all treated animals demonstrated fetal death and resorption. Conception rates were, however, unaffected. Therefore, diabetes was induced well in advance of conception in this species, eliminating the diabetogenic drug as a factor in the fetal effects while maintaining the benefits of large numbers for evaluation.

Animals↗
PubMed1980

The effect of long-distance running on plasma immunoreactive glucagon levels.

Twelve highly conditioned long-distance runners were studied to determine the effects of marathon (42 km) and 10,000 m running on plasma immunoreactive glucagon (IRG), serum immunoreactive insulin (IRI), and serum glucose (G) levels. Blood samples were drawn just prior to and immediately upon completion of the run. Marathon running resulted in no significant change in G, IRI, or IRG levels. After running 10,000 m, plasma IRG levels did not change significantly, while IRI and G increased significantly. In evaluating the pooled data from both runs, a significant inverse correlation was observed between delta G and delta IRG. This relationship between delta G and delta IRG suggests that glucagon plays a role in maintaining normal blood glucose levels during strenuous exercise.

Adult↗
PubMed1980

Glucose tolerance an insulin release in L-asparaginase treated rabbits.

Male New Zealand White Rabbits were injected intravenously with either a single dose of 10,000 IU Escherichia coli L-asparaginase/kg body weight containing 80 mg of D-mannitol/10,000 IU E. coli L-asparaginase or 80 mg D-mannitol kg/body weight alone. Elevated fasting glucose (G) and elevated fasting immunoreactive insulin (IRI) levels were observed in the L-asparaginase treated rabbits at 1 wk. They peaked at 3 wk and declined thereafter. However, fasting G and IRI levels remained significantly elevated at the end of the study (9-15 wk after injection) compared to preinjection levels and levels of the controls. Glucose and IRI levels 0.5 hr post and intravenous glucose load (1 g/kg body weight) also became elevated post L-asparaginase and followed a time course similar to that of the fasting G and IRI levels. These 0.5-hr levels also remained significantly elevated at the end of the study. These data show that a single dose of 10,000 IU/kg body weight produced a hyperinsulinemic diabetes in New Zealand White Rabbits that appears to persist in a mild form for at least 9-15 week.

Animals↗
PubMed1980

L-Asparaginase-induced diabetes mellitus in rabbits.

Twenty-seven male New Zealand White rabbits were injected with a single dose of 10,000 IU E. coli L-asparaginase per kilogram body wt to document the diabetogenic activity of this antitumor agent. Significant weight loss was observed by day 1, and a loss continued until day 9. After day 16, weight steadily increased. Random serum glucose levels increased steadily after the injection of L-asparaginase, reaching a peak value of 344 +/- 32 mg/dl (x- +/- SEM) on day 10. From day 12, levels declined, but they remained significantly higher than basal levels. Serum immunoreactive insulin (IRI) levels had a similar pattern of response. By day 2 the IRI was significantly above baseline. The IRI levels increased daily, reaching a peak level of 1,379 +/- 587 pg/ml (x- +/- SEM). Thereafter the levels fell gradually. However, the IRI levels remained significantly higher than basal levels. Intravenous regular insulin decreased glucose levels in L-asparaginase-treated animals at 3 h by only 7.7 +/- 3.2%, while it decreased them in controls by 34.0 +/- 6.7% (P less than 0.0025). These data demonstrate that, acutely, a single intravenous dose of 10,000 IU E. coli L-asparaginase per kilogram body wt induces a hyperinsulinemic. Insulin-resistant, diabetic syndrome in rabbits.

Animals↗
PubMed1978

The effect of E. coli L-asparaginase on oral glucose tolerance and insulin release in man.

To study the effect of E. Coli L-asparaginase on glucose tolerance and insulin release, 6 patients with neoplastic disease were subjected to 3 hour oral glucose tolerance tests with simultaneous measurement of serum immunoreactive insulin (IRI) levels before and following the intravenous administration of 5000 I. U. L-asparaginase/day for 4 days. Five of the patients exhibited a significant deterioration in glucose tolerance; however, no change was noted in their fasting glucose and IRI levels. The deterioration in glucose tolerance was associated with a decrease in the amount of insulin secreted in the first 30 minutes after the oral glucose load. The total amount of insulin released during the 3 hour test remained unchanged. These studies suggest that L-asparaginase can cause a deterioration of glucose tolerance without accompanying fasting hyperglycaemia. This may be due, in part, to a decrease in glucose-induced insulin release during the first thirty minutes following oral glucose.

Adult↗
PubMed1977

Insulin-dependent diabetes mellitus. Sudden onset following hypophysectomy in an acromegalic patient.

A euglycemic woman with acromegaly contracted conspicuous hyperglycemia two hours following transphenoidal hypophysectomy. Insulin therapy was initiated and has by necessity been continued. The development in the immediate postoperative period of blood glucose levels ranging from 300 to 500 mg/dl was totally unexpected, as the levels on the preoperative oral glucose tolerance test were normal. No explanation for this sudden development of hyperglycemia is apparent. Therefore, frequent monitoring of the blood glucose level is necessary in all acromegalic patients following hypophysectomy, even if they are euglycemic prior to surgery.

Acromegaly↗
PubMed1977

Functional abnormalities of islets of Langerhans of obese hyperglycemic mouse.

Glucose-induced insulin release was studied in vitro with isolated islets of Langerhans obtained from obese hyperglycemic C57Bl/6J-ob/ob (ob/ob) and lean C57Bl/6J-+/+ (control) mice. The threshold concentrations of glucose for insulin release were determined. In addition, the effect of total fast and of chronic food restriction on in vitro insulin release were studied. The following was observed: 1) with fasting, islet volume decreased. Islets obtained from ob/ob mice were larger than control islets, except for the chronic food restricted group. 2) Ob/ob islets were more sensitive to glucose than were controls in that the threshold for glucose-induced insulin release occured at lower glucose concentrations. 3) Fasting for 48 h completely abolished glucose-induced insulin release in control islets, whereas glucose-induced insulin release was maintained in 48-h and 7-day fasted ob/ob islets. 4) The increased glucose sensitivity of the ob/ob islets was maintained despite chronic food restriction.

Animals↗
PubMed1977

Half life of injected 125I-insulin in control and ob/ob mice.

The t-1/2 of moniodo 125I-insulin in ob/ob mice and their lean litter mates is 10 min. No difference was found between the two groups. Further, 48 hr of fasting did not alter the t-1/2 in ob/ob mice. In view of the markedly enlarged insulin pool in ob/ob mice, one must conclude that the mass of insulin degraded in unit time is increased. However, these findings indicate that the cause of hyperinsulinism in ob/ob mice is unrelated to rates of insulin degradation.

Animals↗
PubMed1976

Plasma immunoreactive glucagon fractions in four cases of glucagonoma: increased "large glucagon-immunoreactivity".

Immunoreactive glucagon (IRG) fractions from plasma of 8 normal subjects and 4 patients with glucagon secreting tumors were studied by gel filtration techniques on Bio Gel P--30 and Sephadex G--50 columns. The pancreatic glucagon specific anti serum (30K) of Unger was utilized to measure IRG. Columns were calibrated with labelled albumin, proinsulin, insulin and glucagon. Four peaks were defined in normal and tumor bearing patients: peak I (greater than 20 000 mol. wt.), peak II (primarily 9000 mol. wt.), peak III pancreatic glucagon (3500 mol. wt.) and peak IV small gucagon (less than 3500 mol. wt.). Glucagonoma patients differed from our normal and reported normal subjects in that peak II contained most of the circulating IRG. The percent of IRG associated with peak II was 9.5--31.5% in normals and 39.1--61.2% in glucagonomas. Glucagon-like biological activity in an isolated hepatocyte system was demonstrated for all peaks. However, relative to immunoreactivity, peak II showed reduced activity (25--33%). Immunoassay of dilutions of all peaks revealed the probability of immuno determinants identical with procine pancreatic glucagon. The presence of heterogenous IRG peaks with biological glucagon-like activity suggest that the larger molecules may be prohormones. Further, it is possible that specific elevation of peak II may be a diagnostic feature of glucagonomas.

Adenoma, Islet Cell↗
PubMed1975

The effect of fasting on tissue cyclic cAMP and plasma glucagon in the obese hyperglycemic mouse.

The effect of 48 h of fasting in C57B1/6J-ob/ob and +/+ mice on body weight (BW), blood glucose (BG), serum immunreactive insulin (IRI), plasma immunoreactive glucagon (IRG) and on tissue levels of cyclic adenosine monophosphate (cAMP) were studied. Both groups of mice lost weight and demonstrated a decrease in BG and IRI with fasting. However, the BG and IRI of the ob/ob animals were initially highter and remained higher than those of the 2% of their initial weight while the +/+ lost 14 %. The +/+ mice exhibited an increase in cAMP levels in skeletal muscle, fat and liver with fasting, while the ob/ob mice had increased levels of cAMP in fat, but not in muscle. They also had a paradoxical decrease in liver cAMP levels with fasting, and associated with this was the lack of stimulation of glycogenolysis. Glycogenolysis was significant in the livers of fasted +/+ mice. The plasma IRG levels of the fed ob/ob mice were significantly higher (1.8) times) than those of the fed +/+ mice. Islet cAMP levels were decreased with fasting in ob/ob mice. However, the levels were significantly higher in 48-h faster ob/ob mice compared to the fasted +/+ group. The apparent paradoxical response to fasting observed in the livers of the ob/ob mice remains unexplained.

Animals↗