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Biomedical subjects

A M Lombardi

Publications and source records attributed to A M Lombardi.

12 recordsLinked to original sources
PubMed2000

Substrate competition and insulin action in animal models.

Increased basal plasma FFA and lactate concentrations are often present in obesity and may deeply affect insulin action. The inhibition of glucose transport or phosphorylation is thought to be involved in this phenomenon, but the molecular mechanisms on the basis are still unknown. In our laboratory we observed that a chronic infusion of Intralipid plus heparin in rats significantly decreased the insulin dependent-glucose uptake, as well as GLUT4 gene expression in muscular tissue. On the other hand it has been shown that an enhanced plasma lactate concentration may increase insulin secretion and hepatic insulin clearance. Moreover we observed that chronic hyperlactatemia in rats is able to decrease glucose uptake in muscles, while reducing GLUT4 mRNA and protein in the same tissues. In obesity, lactate and FFA overproduction from visceral fat may therefore play a synergic role in reducing insulin sensitivity.

Adipose Tissue↗
PubMed1999

Leptin concentration in newborns' cord blood: relationship to gender and growth-regulating hormones.

AIMS: To verify if plasma leptin concentrations of newborns at birth differ significantly between sexes; and to investigate the potential interactions between plasma leptin and growth-regulating hormones at birth. SUBJECTS: 98 healthy newborns (48 male, 50 female) were studied. Leptin, insulin, cortisol, insulin-like growth factor-1 (IGF-1), testosterone, and sex hormone binding globulin (SHBG) concentrations were measured from venous blood collected from the umbilical cord vein immediately after birth. RESULTS: The serum leptin concentration of newborns averaged 8.05(0.5) ng/ml. Females had significantly (P<0.005) higher serum leptin values than males [9. 6(0.8) vs 6.0(0.6) ng/ml]. IGF-1 was significantly (P<0.05) higher in females than in males [87(4) vs 74(5) microg/l], whereas SHBG was slightly lower [29(1) vs 33(2) nmol/l]. Insulin, cortisol, and testosterone serum concentrations were not statistically different between the sexes. Among the variables examined, birth weight (expressed as Z-score of weight) and insulin showed the highest degree of relationship with serum leptin in newborns (r=0.48 and r=0.31 respectively, P<0.001). Multiple regression analysis showed that Z-score of birth weight, gender and cortisol were able to account for approximately 44% of inter-individual variability of serum leptin concentrations in newborns. CONCLUSIONS: Female newborns have significantly higher serum leptin concentrations than males. Insulin, IGF-1, testosterone, and SHBG did not independently affect leptin inter-individual variability when gender, Z-score of body weight, and cortisol were taken into account. Other factors may be involved in the differences in circulating leptin concentrations between the sexes in newborns.

Female↗
PubMed1999

Hyperlactatemia reduces muscle glucose uptake and GLUT-4 mRNA while increasing (E1alpha)PDH gene expression in rat.

An increased basal plasma lactate concentration is present in many physiological and pathological conditions, including obesity and diabetes. We previously demonstrated that acute lactate infusion in rats produced a decrease in overall glucose uptake. The present study was carried out to further investigate the effect of lactate on glucose transport and utilization in skeletal muscle. In chronically catheterized rats, a 24-h sodium lactate or bicarbonate infusion was performed. To study glucose uptake in muscle, a bolus of 2-deoxy-[3H]glucose was injected in basal condition and during euglycemic-hyperinsulinemic clamp. Our results show that hyperlactatemia decreased glucose uptake in muscles (i.e., red quadriceps; P < 0.05). Moreover in red muscles, both GLUT-4 mRNA (-30% in red quadriceps and -60% in soleus; P < 0.025) and protein (-40% in red quadriceps; P < 0.05) were decreased, whereas the (E1alpha)pyruvate dehydrogenase (PDH) mRNA was increased (+40% in red quadriceps; P < 0.001) in lactate-infused animals. PDH protein was also increased (4-fold in red gastrocnemius and 2-fold in red quadriceps). These results indicate that chronic hyperlactatemia reduces glucose uptake by affecting the expression of genes involved in glucose metabolism in muscle, suggesting a role for lactate in the development of insulin resistance.

Animals↗
PubMed1997

Lactate infusion in anesthetized rats produces insulin resistance in heart and skeletal muscles.

Plasma lactate is elevated in many physiological and pathological conditions, such as physical exercise, obesity, and diabetes, in which a reduction of insulin sensitivity is also present. Furthermore, an increased production of lactate from muscle and adipose tissue together with increased gluconeogenic substrate flux to the liver plays a primary role in enhancing hepatic glucose production (HGP) in diabetes. It has been shown that lactate may interfere with the utilization and oxidation of other substrates such as free fatty acids (FFAs). The aim of this study was to investigate if lactate infusion affects peripheral glucose utilization in rats. Animals were acutely infused with lactate to achieve a final lactate concentration of 4 mmol/L. They were then submitted to a euglycemic-hyperinsulinemic clamp to study HGP and overall glucose metabolism (rate of disappearance [Rd]). At the end of the clamp, a bolus of 2-deoxy-[1-3H]-glucose was injected to study insulin-dependent glucose uptake in different tissues. The results show that lactate infusion did not affect HGP either in the basal state or at the end of clamp, whereas glucose utilization significantly decreased in lactate-infused rats (26.6 +/- 1.1 v 19.5 +/- 1.4 mg.kg-1.min-1, P < .01). A reduction in the tissue glucose utilization index was noted in heart (18.01 +/- 4.44 v 46.21 +/- 6.51 ng.mg-1.min-1, P < .01), diaphragm (5.56 +/- 0.74 v 9.01 +/- 0.93 ng.mg-1.min-1, P < .01), soleus (13.62 +/- 2.29 v 34.05 +/- 6.08 ng.mg-1.min-1, P < .01), and red quadricep (4.43 +/- 0.73 v 5.88 +/- 0.32 ng.mg-1.min-1, P < .05) muscle in lactate-infused animals, whereas no alterations were observed in other muscles or in adipose tissue. Therefore, we suggest that acute lactate infusion induces insulin resistance in the heart and some muscles, thus supporting a role for lactate in the regulation of peripheral glucose metabolism.

Adipose Tissue↗
PubMed1997

Phenotype of transgenic mice overexpressing GLUT4 and hexokinase II in muscle.

To optimize glucose utilization, double transgenic mice were created by crossing mice overexpressing glucose transporter GLUT4 with mice overexpressing hexokinase (HKII) in muscle. Transgenic mice overexpressing GLUT4 alone have exhibited improvements in glucose tolerance and insulin action. In vitro studies of hexose uptake in soleus muscle from transgenic mice suggested that GLUT4 was limiting the glucose flux except at high glucose concentration, where hexokinase became the limiting step. In vivo, glucose tolerance was similar in GLUT4 and GLUT4/HKII mice, although stimulated plasma insulin values were significantly lower in the latter group. Insulin tolerance tests performed in diabetic GLUT4 vs. diabetic GLUT4/HKII transgenic mice yielded identical results. Again, endogenous insulin in GLUT4/HKII mice during a mild hyperglycemic clamp was stimulated by only two- vs. fourfold in GLUT4 mice. Although the overexpression of HKII alone resulted in increased glucose utilization in several muscles, the overexpression of GLUT4 plus HKII did not augment basal or stimulated in vivo glucose utilization compared to GLUT4 overexpression. In conclusion, GLUT4 is rate limiting for muscle glucose utilization but HKII might be important under hyperglycemia. The addition of HKII to GLUT4 overexpression is not sufficient to further augment glucose tolerance or insulin action. In GLUT4/HKII double transgenic mice, glucose clearance is tempered by a low insulin stimulated level.

Animals↗
PubMed1997

Lactate infusion to normal rats during hyperglycemia enhances in vivo muscle glycogen synthesis.

Both hyperglycemia and hyperinsulinemia stimulate whole body and muscle glucose disposal. To define the impact of increased lactate concentration (4-5 mM) on muscle glucose disposal during hyperglycemia, we studied anesthetized normal rats infused with either sodium lactate or sodium bicarbonate as control. Animals were studied under hyperglycemic clamp (13 mM) using [3-3H]glucose (study 1) and 2-deoxy-[1-3H]glucose (study 2) to assess glucose rate of disappearance (Rd), glycolytic flux (GF), glycogen synthesis, and glucose utilization index by different tissues. Moreover, in study 3, the effect of lactate on the pattern of plasma insulin response to hyperglycemia was evaluated. In study 1, lactate infusion resulted in an increased Rd (38.7 +/- 1.7 vs. 32.3 +/- 1.3 mg.min-1.kg-1; P < 0.01), which was explained by an enhanced rate of glycogen synthesis (23.0 +/- 1.7 vs. 14.7 +/- 1.2 mg.min-1.kg-1; P < 0.001), whereas GF was unchanged. In study 2, lactate-infused animals showed an increased 2-deoxy-glucose disposal and a stimulated glycogen synthase activity as well as an increased glycogen accumulation at the end of the study in several skeletal muscles. In study 3, lactate did not induce any change in either early or late insulin response to hyperglycemia. In conclusion, our results show that muscle glycogen deposition may be enhanced by elevated lactate levels under hyperglycemic conditions and support a role for lactate in the regulation of glucose homeostasis.

Animals↗
PubMed1996

Effect of lactate on hepatic insulin clearance in perfused rat liver.

The aim of our study was to investigate whether sodium lactate has any effect on hepatic insulin dynamics in perfused rat liver. Rat livers were perfused in situ with saline or increasing concentrations of sodium lactate, and hepatic insulin extraction was calculated from the difference in insulin concentration between the portal and the suprahepatic vein. Our results show that hepatic insulin extraction at the three lactate concentrations added was higher than in the control experiments (lactate 1 mmol/l: 263 +/- 51 vs. 765 +/- 114, P < 0.005; lactate 5 mmol/l: 341 +/- 80 vs. 906 +/- 109; P < 0.005; lactate 15 mmol/l: 438 +/- 21 vs. 981 +/- 66 microIU.g-1.30 min-1, P < 0.005). No significant differences were observed in net glucose balance across the liver during perfusion with lactate. Moreover perfused liver displayed a net lactate production during infusion with saline or lactate added at the lower concentrations (1 and 5 mM), whereas at the highest (15 mM), a net lactate uptake by the liver was observed (P < 0.05). Our results suggest that, in perfused rat liver, lactate may increase hepatic insulin clearance. Thus energy fuels such as lactate and nonesterified fatty acid have opposite effects on hepatic insulin clearance and may therefore contribute to the regulation of posthepatic insulin delivery.

Animals↗
PubMed1994

[Aarskog syndrome. A case report].

A case of Aarskog syndrome in a 10-year-old boy born to an epileptic woman is reported. Clinical features and genetics of the condition are reviewed. An underestimated incidence of the syndrome related to its mild phenotypical appearance is suggested. Finally the association between Aarskog syndrome and maternal epilepsy is discussed.

Abnormalities, Multiple↗
PubMed1993

Lipolytic effect of beta-endorphin in human fat cells.

Recently, a role of beta-Endorphin on peripheral tissue metabolism has been suggested. A lipolytic effect of beta-Endorphin has been observed both in vivo and in vitro in animals but, at present, there is no evidence for a similar effect in humans. In this study, we investigated the lipolytic effect of beta-Endorphin in isolated human adipocytes. beta-Endorphin induced a significant increase in glycerol release in isolated human fat cells. Naloxone was able to inhibit the beta-Endorphin-induced lipolysis. The opioid antagonist alone had no effect on basal lipolysis and on Epinephrine-stimulated lipolysis when administered together with this hormone. Our results suggest that beta-Endorphin may play a role on lipolysis also in human fat cells and that this effect may be mediated by a specific opiate receptor.

Adipose Tissue↗
PubMedDate not supplied

Microsatellite alterations in uterine leiomyomas.

Recent studies have shown that microsatellites instability (MI) has a leading role in the development of different types of cancer: a high rate of di-tri or tetranucleotide repeats have been found in familial polyposis and in sporadic colorectal, gastric, breast and endometrial carcinomas. In the present study, we selected the DNA of 23 histological samples from patients with uterine leimyomas, aged between 24 and 65 years. The negative portion was divided from the pathological portion in the same sample of each patient. Each sample was analyzed for 7 microsatellites (D25123, Mfd39, 635. 636. Mfd67, D11S905, SCZD1 and DM) through double amplification with the PCR using external and internal primer couples. Seven of 23 samples analyzed on the denaturant gel of acrylamide (30.4%) were positive for microsatellite alterations. The recurrence of these alterations, which appear in our study, suggest their involvement in benign transformation of smooth muscle cells.

Adult↗