Failure of fenfluramine to affect basal and insulin-stimulated hexose transport in rat skeletal muscle

Sasson, Shlomo; Kunievsky, Baruch; Nathan, C.; Cerasi, Erol

doi:10.1016/0006-2952(89)90551-0

Cited by 7 publications

(7 citation statements)

References 20 publications

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“…Nevertheless, in agreement with Randle's cycle concept (30), which has been exemplified in obesity and NIDDM (24,31,32), we hypothesized that the lower FFA plasma levels observed after d-fenfluramine may be at least partially responsible for the better insulin action on glucose disposal. Such an indirect mechanism would be consistent with in vitro studies showing the failure of fenfluramine to affect basal and insulin-stimulated hexose transport in rat skeletal muscle (33).…”

Section: Discussionsupporting

confidence: 69%

Improvement of Insulin-Induced Glucose Disposal in Obese Patients With NIDDM After 1-Wk Treatment With d-Fenfluramine

Scheen¹,

Paolisso²,

Salvatore³

et al. 1991

Diabetes Care

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Section: Discussionsupporting

confidence: 69%

Improvement of Insulin-Induced Glucose Disposal in Obese Patients With NIDDM After 1-Wk Treatment With d-Fenfluramine

Scheen¹,

Paolisso²,

Salvatore³

et al. 1991

Diabetes Care

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“…These observations with benfluorex are in line with those reported with the related compound, fenfluramine, suggesting a failure of the drug to affect in vitro basal and insulin-stimulated glucose transport in rat skeletal muscle (16,17) or a very marginal ability to ameliorate insulin resistance induced by fat feeding in skeletal muscles and white adipose tissues (5,18,19).…”

Section: Discussionsupporting

confidence: 81%

Benfluorex Normalizes Hyperglycemia and Reverses Hepatic Insulin Resistance in STZ-Induced Diabetic Rats

1993

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We have examined the effect of chronic (20 days) oral administration of benfluorex (35 mg/kg) in a rat model of NIDDM, induced by injection of STZ 5 days after birth and characterized by frank hyperglycemia, hypoinsulinemia, and hepatic and peripheral insulin resistance. We assessed the following: 1) basal blood glucose and insulin levels, 2) glucose tolerance and glucose-induced insulin release in vivo and in vitro, and 3) basal and insulin-stimulated in vivo glucose production and glucose utilization, using the insulin-clamp technique in conjunction with isotopic measurement of glucose turnover. The in vivo insulin response of several individual tissues also was evaluated under the steady-state conditions of the clamp, using the uptake of the glucose analogue 2-deoxy-D-glucose as a relative index of glucose metabolism. In the benfluorex-treated diabetic rats, postabsorptive basal plasma glucose levels were decreased (8.1 +/- 0.2 mM compared with 10.5 +/- 0.5 mM in the pair-fed untreated diabetic rats and 6.1 +/- 0.2 mM in the benfluorex-treated nondiabetic rats), whereas the basal and glucose-stimulated intravenous glucose tolerance test plasma insulin levels were not improved. Such a lack of improvement in the glucose-induced insulin release after benfluorex treatment was confirmed under in vitro conditions (perfused pancreas). In the pair-fed untreated diabetic rats, the basal glucose production and overall glucose utilization were significantly increased, and during hyperinsulinemia both liver and peripheral tissues revealed insulin resistance. In the benfluorex-treated diabetic rats, the basal glucose production and basal overall glucose utilization were normalized. After hyperinsulinemia, glucose production was normally suppressed, whereas overall glucose utilization was not significantly improved.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The uptake of | ,H|-2D-Glu ex vivo was determined based on a modification of the method described by Sasson et al [22]. Cerebral hemispheres (about 120 mg wet weight) from either restricted or sham-operated fetuses were cut into two halves to improve perfusion and rinsed 3 times with PBS at ambient temperature.…”

Section: Ijh1-2d-gltt Uptakementioning

confidence: 99%

“…the radioactivity was counted in 20 ml Luniax-xylene mixture using the (3H/MC) channel ratio setting of a Packard Tricarb (3-counter. Data was normalized to wet weight and values corrected for the extracellular space [22].…”

Section: Restriction Reperfusionmentioning

confidence: 99%

Transient Rise of Glucose Uptake in the Fetal Rat Brain after Brief Episodes of Intrauterine Ischemia

Kunievsky¹,

Pretsky²,

Yavin³

1994

Dev Neurosci

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In a rat model of intrauterine growth retardation and fetal brain ischemia, the maternal-fetal circulation was obstructed for up to 40 min in 20-day gestational age rats by occluding (restriction) the uterine blood vessels supplying the placenta. After restriction, flow was returned (reperfusion) for designated times. A time-dependent depletion of cerebral pyruvate levels (from 0.2 ± 0.02 to 0.06 ± 0.01 pmol/g wet weight) accompanied by an elevation in lactate concentration (from 1.95 ± 0.03 to 7.00 ± 0.56 umol/g wet weight) was observed after 20 min restriction. During 20 min, reperfusion lactate levels continued to increase, then gradually decreased as the reperfusion continued for approximately 2 h. A drastic increase in the lactate/pyruvate ratio (from 10 to 117) suggested that the fetal brain was relying on anaerobic glycolysis to meet its energy demands. In addition, a time-dependent decrease in fetal brain phosphocreatine (PCr) content from 2.54 ± 0.26 to 1.52 ± 0.15 mM was observed after 20 min of maternal-fetal blood flow obstruction. ATP levels gradually decreased after 20 min restriction from 1.62 ± 0.13 to 0.59 ± 0.09 mM. After 30 min reperfusion ATP, PCr and pyruvate returned to their normal values. These metabolic changes observed are concordant with the ability of the ischemic fetal brain to sustain adequate levels of ATP for energy-requiring cellular processes. The capacity of glucose transporters to facilitate transport of glucose into brain tissue was assessed ex vivo, using [³H]2-deoxyglucose (2D-Glu). A statistically significant increase of 2D-Glu uptake, from 48.9 ± 2.3 to 69.5 ± 4.5 pmol/mg (42%) was noticed in fetal brains after 20 min restriction. Kinetic analysis revealed a 2.2-fold increase in the maximal uptake of [³H]-2D-Glu after 20 min blood flow restriction. Facilitation of specific glucose transporters triggered by oxygen depletion and glucose reduction, may contribute to the partial resistance of the fetal brain to ischemia and account for the moderate decrease in ATP energy levels.

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Failure of fenfluramine to affect basal and insulin-stimulated hexose transport in rat skeletal muscle

Cited by 7 publications

References 20 publications

Improvement of Insulin-Induced Glucose Disposal in Obese Patients With NIDDM After 1-Wk Treatment With d-Fenfluramine

Improvement of Insulin-Induced Glucose Disposal in Obese Patients With NIDDM After 1-Wk Treatment With d-Fenfluramine

Benfluorex Normalizes Hyperglycemia and Reverses Hepatic Insulin Resistance in STZ-Induced Diabetic Rats

Transient Rise of Glucose Uptake in the Fetal Rat Brain after Brief Episodes of Intrauterine Ischemia

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