.p.m.) and the supernatant was treated with Chelex-100 resin and then lyophilised. Assessment of glucose metabolism by NMR spectroscopy The lyophilised cell extracts were dissolved in 3 ml H 2 O and then centrifuged at 1500
S Patterson, P R Flatt, L Brennan, P Newsholme and N H McClenaghan
Anthony Raffo, Kolbe Hancock, Teresa Polito, Yuli Xie, Gordon Andan, Piotr Witkowski, Mark Hardy, Pasquale Barba, Caterina Ferrara, Antonella Maffei, Matthew Freeby, Robin Goland, Rudolph L Leibel, Ian R Sweet and Paul E Harris
tissue and β-cells, in glucose metabolism has not yet been explored. As indicated, endogenously synthesized and/or stored monoamine neurotransmitters appear to participate in the paracrine regulation of insulin secretion and entrainment of the activity of
Yu Wu, Tingting Wu, Jun Wu, Lei Zhao, Qing Li, Zac Varghese, John F Moorhead, Stephen H Powis, Yaxi Chen and Xiong Z Ruan
aggravated insulin resistance and glucose metabolism disorders in HFD-fed C57BL/6J mice The fasting glucose levels were unchanged in HFD-fed mice compared with NCD-fed mice ( Fig. 2 A and C). After glucose challenge, blood glucose concentration of HFD group
Mariana Rosolen Tavares, Simone Ferreira Lemes, Thais de Fante, Cristina Saenz de Miera, Isadora Carolina Betim Pavan, Rosangela Maria Neves Bezerra, Patricia Oliveira Prada, Marcio Alberto Torsoni, Carol Fuzeti Elias and Fernando Moreira Simabuco
modulate hepatic glucose metabolism As hypothalamic S6K1 may control glucose homeostasis ( Ono et al. 2008 , Smith et al. 2015 ), we sought peripheral changes resulting from the S6Ks modulation in the hypothalamus. Mice with overexpression of
Rengasamy Palanivel, Vivian Vu, Min Park, Xiangping Fang and Gary Sweeney
contractile performance is derived from fatty acids while the remainder (∼30%) is principally obtained via metabolism of glucose ( Stanley et al . 2005 , An & Rodrigues 2006 ). Well-controlled fatty acid metabolism is also important to prevent triglyceride
M.-Th Sutter-Dub, A. Sfaxi and P. Strozza
Pregnancy and progesterone treatment of ovariectomized rats decrease glucose metabolism through the pentose-phosphate pathway in isolated female rat adipocytes. As demonstrated in previous studies, progesterone directly decreases [1-14C]glucose oxidation through the pentose-phosphate pathway and lipogenesis from [6-14C]glucose; the present study therefore compared glucose-induced lipid synthesis during pregnancy (10, 16 and 20 days of pregnancy) with the effect of progesterone treatment (5 mg/rat per day for 14 days) to shed more light on the role of this steroid in glucose metabolism during pregnancy. The inhibition of [6-14C]glucose incorporation into triacylglycerols in the progesterone-treated rats was comparable to that which occurs during late (20 days) and mid-pregnancy (16 days) but not during early pregnancy (10 days). The inhibition of fatty acid synthesis was more important as pregnancy advanced and was different from the decrease in fatty acid synthesis induced by progesterone treatment. The sensitivity to insulin was comparable in virgin, ovariectomized and progesterone-treated ovariectomized rats but not in pregnant rats. This implies that progesterone and insulin affect glucose-induced lipid synthesis by distinct processes and that the impaired glucose metabolism is characterized by a reduction in basal glucose utilization rather than by an impaired insulin response.
I. M. D. JACKSON, C. R. M. PRENTICE and MARGARET T. McKIDDIE
Although the clinical association of hypothyroidism and diabetes mellitus is well known (Phair, Bondy & Abelson, 1965; Hecht & Gershberg, 1968) there have been few studies of glucose and insulin metabolism in hypothyroidism before and after treatment; this paper reports our findings in ten such subjects.
Ten patients (9 female, 1 male; aged 43–73 yr.) with obvious clinical hypothyroidism, due to primary thyroid failure confirmed by a combination of serum protein-bound iodine, radioactive iodine studies with thyroid-stimulating hormone stimulation (as appropriate) and thyroid antibody studies, were investigated. None were known to be diabetic. An oral glucose tolerance test (50 g.) before and after treatment was performed, venous blood being removed for determination of blood sugar and plasma insulin levels at 0, 30, 60, 90 and 120 min. The sugar was measured as total reducing substances in a Technicon auto-analyser and plasma insulin by the double antibody radioimmunoassay method of Hales
A. Klein, A. W.-L. Chan and A. Malkin
Mononuclear cell preparations are capable of metabolizing cortisol to three metabolites which lack the immunosuppressive effect of their precursor. In the present study we noted a linear correlation, up to a point, between glucose concentration and the rate of human mononuclear cell cortisol metabolism in vitro. The mechanism by which glucose exerts its effect was investigated further. We observed that: (1) the effect of glucose on mononuclear cell cortisol metabolism was not influenced by insulin; (2) NADPH and NADH enhanced cortisol metabolism by disrupted cells, irrespective of whether the homogenates were dialysed or not; (3) lactate and ATP inhibited mononuclear cell cortisol metabolism and (4) almost all the glucose used was converted to lactate. It is concluded that mononuclear cell cortisol metabolism can depend on both nucleotides.
J. Endocr. (1986) 109, 181–185
J. C. Escolar, R. Hoo-Paris, Ch. Castex and B. Ch. J. Sutter
The direct effect of hypothermia on the inhibition of insulin secretion may result from inhibition of the availability of energetic substrates and/or the lack of metabolic signals. In order to verify this hypothesis, the insulin secretion and the main metabolic glucose pathways were measured during the incubation of rat islets. In the presence of 16·7 mmol glucose/l and at 37 °C, insulin secretion was 925 ± 119 μU/2 h per ten islets. With the same experimental conditions, glucose utilization, determined as the formation of 3H2O from [5-3H]glucose was 2225 ±184 pmol/2 h per ten islets, glucose oxidation measured as the formation of 14CO2 from [U-14C]glucose was 673 ± 51 pmol/2 h per ten islets, pentose cycle determined as the formation of 14CO2 from either [1-14C]glucose or [6-14C]glucose was 37 ± 5 pmol/2 h per ten islets; glucose oxidation by the tricarboxilic acid cycle, calculated to be the difference between glucose oxidation and pentose cycle values, was 636 pmol/2 h per ten islets.
Hypothermia highly inhibited glucose-induced insulin secretion and glucose utilization. Inhibition of insulin secretion was partial at 27 °C since it was 2·5 times lower than that at 37 °C, and it was complete at 17 °C. Glucose oxidation in the tricarboxilic acid cycle was markedly inhibited by hypothermia since the inhibition coefficient (Q10) between 37 and 27 °C was 5. In contrast, glucose oxidation in the pentose phosphate shunt was enhanced at 27 °C, reaching 92 ± 17 pmol/2 h per ten islets, and it was inhibited relatively little at 17 °C.
These results suggest that hypothermia markedly inhibits glucose metabolism with the exception of the pentose pathway which could play an important role by inducing the insulin secretion at 27 °C.
Journal of Endocrinology (1990) 125, 45–51
S Ranganathan and PA Kern
Treatment of HIV infection using protease inhibitors is frequently associated with lipodystrophy and impaired lipid and glucose metabolism. We examined the effect of saquinavir, one of the protease inhibitors, on lipid metabolism and glucose transport in cultured adipocytes. Saquinavir inhibited lipoprotein lipase (LPL) activity in 3T3-F442A and 3T3-L1 adipocytes. The inhibition of LPL was 81% at a concentration of 20 microg/ml. Another closely related drug, indinavir, had a small inhibitory effect. Saquinavir also inhibited the biosynthesis of lipids from [(14)C]-acetate. Saquinavir increased the lipolysis. Saquinavir had no significant effect on the cellular protein synthesis or protein content. Saquinavir increased the basal glucose transport threefold and decreased insulin-stimulated glucose transport by 35%. These studies suggest that some HIV protease inhibitors have direct effects on lipid and glucose metabolism. This inhibition of lipogenesis and glucose transport may explain some of the lipodystrophy, dyslipidemia and disturbed glucose metabolism with the clinical use of these drugs.