plasma leptin and resistin were determined by the ELISA technique according to the manufacturer's instructions (R&D Systems, Minneapolis, MN, USA). Measurements of cellular respiration and the rate of glycolysis A XF24 Seahorse Bioscience instrument
Eun Hee Koh, Ah-Ram Kim, Hyunshik Kim, Jin Hee Kim, Hye-Sun Park, Myoung Seok Ko, Mi-Ok Kim, Hyuk-Joong Kim, Bum Joong Kim, Hyun Ju Yoo, Su Jung Kim, Jin Sun Oh, Chang-Yun Woo, Jung Eun Jang, Jaechan Leem, Myung Hwan Cho, and Ki-Up Lee
J. Hinson and M. K. Birmingham
The effects of shortening the ACTH molecule from either end of the peptide chain on adrenal glycolysis and steroidogenesis were examined in mouse adrenal cell suspensions. Shortening the (1–24) sequence to (1–17), (1–16) and (1–14), thereby interfering with the basic tetrapeptide (15–18) assigned to the address message, progressively reduced both glycolytic and steroidogenic potencies by four, six and ten orders of magnitude respectively, without impairing the capacity for maximal excitation. The glycolytic potency of the (1–18) sequence, which was amidated at the C-terminal, equalled that of ACTH(1–24), but the steroidogenic potency was reduced by an order of magnitude. The (1–13) sequence of α-MSH, which contains substitutions at both terminals, had glycolytic and steroidogenic potencies intermediate between those of ACTH(1–16) and ACTH(1–17). Deletion of Ser1,Tyr2 from ACTH(1–18)-NH2 reduced both potencies by an order of magnitude. ACTH(11–24) and (7–38) were inactive or inhibitory.
The capacity for excitation was further examined by comparing responses to peptide fragments (1–4), (1–10), (1–13), (4–10), (4–11), (5–10), (5–14), (7–13) and (11–24) at a concentration of 1 mmol/l. All fragments, excepting (1–4), (5–10) and (11–24) were active. The activities of fragments (5–14) and (7–13), as opposed to (5–10), suggest that the requirements for methionine in position 4 may be replaced by the (11–13) tripeptide. The relative glycolytic responses of fragments containing the (11–13) sequence exceeded the steroidogenic responses, suggesting that the (11– 13) sequence may be specifically implicated in a receptor involved in glycolysis. With this exception, the functional domains within the ACTH molecule responsible for excitation, potentiation and affinity appear to be in similar locations for both evocation of glycolysis and steroidogenesis, judging from the parallel responses to reduction in chain length.
J. Endocr. (1987) 115, 71–76
J. Hinson and M. K. Birmingham
The structural requirements in the ACTH molecule for evocation of the glycolytic response in suspensions of mouse adrenal cells were investigated by examining the effects of analogues containing modifications at positions 8,9 and 10 and of peptides containing homologies with the amino-terminal segment of ACTH. Introduction of a nitrophenylsulphenyl (NPS) group into the tryptophan moiety at position 9 of ACTH(1–24) greatly reduced both the potency and the capacity for maximal glycolytic response. It also virtually abolished cyclic AMP formation. In contrast, the capacity for a maximal steroidogenic response remained unimpaired in the NPS derivative, although steroidogenic potency was reduced to 0·4% of that of ACTH(1–24).
Replacement of the tryptophan moiety with phenylalanine had intermediate inhibitory effects on glycolysis and steroid output; replacement with alanine virtually abolished both these responses. Replacement of arginine in position 8 with lysine in the Phe9 analogue caused a fifty-fold increase in glycolytic potency, but rendered it steroidogenically inactive. Cyclic AMP production was abolished in the Ala9 analogue and greatly impaired in the Phe9 and Lys8,Phe9 analogues. Replacement of the glycine moiety in position 10 with l-alanine, d-alanine, β-alanine or α-aminoisobutyric acid had little or no effect on steroidogenic or glycolytic capacity, although potency was reduced with all substitutions excepting l-alanine.
Vasoactive intestinal peptide, which contains homologies with positions 3, 7, 15 and 16 of ACTH, proved completely inactive in dispersed mouse adrenal cells under our experimental conditions, in contrast to human parathyroid hormone(1–34) (hPTH (1–34)) which contains homologies with positions 3, 4, 5, 9 and 11 and was steroidogenic at the lowest concentration tested (0·1 nmol/l), eliciting an eleven-fold increase in steroid production, a response which might be physiologically relevant. It induced near maximal steroidogenesis at a concentration of 10 nmol/l, without affecting cyclic AMP production, and stimulated glycolysis at concentrations above 10 nmol/l, accompanied by a slight rise in cyclic AMP levels.
The examples of dissociation between glycolysis and steroidogenesis suggest that different receptors may mediate the two responses. The examples of increased steroidogenesis unaccompanied by a rise in cyclic AMP accord with the concept that cyclic AMP is not an obligatory second messenger for the steroidogenic response.
J. Endocr. (1987) 115, 61–69
L. F. B. P. Costa Rosa, Y. Cury, and R. Curi
In the present study the effects of insulin, glucocorticoids and thyroid hormones on macrophage metabolism and function were investigated. The maximum activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase and citrate synthase were determined in macrophages obtained from hormonetreated rats and those cultured for a period of 48 h in the presence of hormones. Macrophage phagocytosis was markedly inhibited by dexamethasone and thyroid hormones, remaining unchanged when insulin was added to the culture medium, however. The changes in the enzyme activities caused by hormone treatments of the rats were very similar to those found in culture. Insulin enhanced citrate synthase and hexokinase activities and diminished those of glutaminase and glucose-6-phosphate dehydrogenase. Dexamethasone had a similar effect except on glucose6-phosphate dehydrogenase. The addition of thyroid hormones to the culture medium raised the activities of glutaminase and hexokinase and reduced that of citrate synthase. The results presented support the suggestion that the effects of insulin, glucocorticoids and thyroid hormones on immune and inflammatory responses could well be mediated through changes in macrophage metabolism..
Journal of Endocrinology (1992) 135, 213–219
Ishita Bakshi, Eurwin Suryana, Lewin Small, Lake-Ee Quek, Amanda E Brandon, Nigel Turner, and Gregory J Cooney
Introduction Reduced levels of glycolysis and glycogen synthesis are a well characterised feature of skeletal muscle in type 2 diabetes ( Bouche et al . 2004 , Abdul-Ghani & DeFronzo 2010 ). In general, the flux through glycolysis is
Y-H Suh, S-Y Kim, H-Y Lee, B C Jang, J H Bae, J-N Sohn, J-H Bae, S-I Suh, J-W Park, K-U Lee, and D-K Song
of glycolysis, we used another insulin secretagogue, methylpyruvate, which bypasses the cytosolic glycolytic pathway and thus directly participates in mitochondrial oxidative phosphorylation to produce ATP ( Dukes et al. 1998 ). The impaired
Fausto Bogazzi, Francesco Raggi, Federica Ultimieri, Dania Russo, Antonella Manariti, Aldo D’Alessio, Paolo Viacava, Giovanni Fanelli, Maurizio Gasperi, Luigi Bartalena, and Enio Martino
-chain fatty acids could be reduced and glycolysis accelerated (el Alaoui-Talibi et al. 1992 , Allard et al. 1999, Wambolt et al. 1999 ). The latter has been proposed as a compensatory response to low fatty acid oxidation ( Allard et al. 1994
Kechun Tang, Teresa Pasqua, Angshuman Biswas, Sumana Mahata, Jennifer Tang, Alisa Tang, Gautam K Bandyopadhyay, Amiya P Sinha-Hikim, Nai-Wen Chi, Nicholas J G Webster, Angelo Corti, and Sushil K Mahata
, Cornelio & Di Donato 1985 ). Both deficiencies are accompanied by reduced anaerobic glycolysis resulting in reduced levels of muscle lactate production, higher serum creatine phosphokinase levels and the presence of histological tubular aggregates (TA) in
Ulrika Bergström, Charlotte Lindfors, Marie Svedberg, Jeanette E Johansen, Jenny Häggkvist, Martin Schalling, Rolf Wibom, Abram Katz, and Ida A K Nilsson
ischemic hypothalamus (~1 min of ischemia). Under this condition, glycolysis (lactate accumulation) was reduced by almost 40%, whereas anaerobic ATP turnover was ~10% lower in the anx/anx group ( Table 2 ). Thus, carbohydrate utilization was diminished
Daniel M Kelly and T Hugh Jones
Insulin signalling ↑ Akt Muscle b Insulin receptor signalling pathway ↑ Protein kinase C Muscle b Insulin receptor signalling pathway ↑ Phosphofructokinase Muscle b Key regulatory enzyme in glycolysis ↑ Hexokinase Muscle b,d,i Key regulatory enzyme in