Hepatic gluconeogenesis and the activity of PDH in individual tissues of GTG-obese mice following adrenalectomy

• Published in: Obesity research Vol. 4; no. 4; pp. 367 - 375
• Main Authors: Blair, S.C. (Royal Prince Alfred Hospital, Camperdown, N.S.W. Australia.), Greenaway, T.M, Bryson, J.M, Phuyal, J.L, Wensley, V.R, Caterson, I.D, Cooney, G.J
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-07-1996
• Subjects: ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; Adrenalectomy; animal models of obesity; Animals; Aurothioglucose; AZUCAR EN SANGRE; Blood Glucose - metabolism; carbohydrate metabolism; CELLULE; CELULAS; Citrate (si)-Synthase - metabolism; Fatty Acids, Nonesterified - blood; FOIE; GLICONEOGENESIS; glucocorticoids; Gluconeogenesis; Glycogen - metabolism; HEMOLIPIDOS; HIGADO; Insulin - blood; INSULINA; INSULINE; Lactic Acid - metabolism; LIPIDE SANGUIN; Liver - anatomy & histology; Liver - metabolism; Male; MEDICAMENT; MEDICAMENTOS; Mice; Mice, Inbred CBA; Mice, Obese; MODELE ANIMAL; MODELOS ANIMALES; NEOGLYCOGENESE; Obesity - chemically induced; Obesity - metabolism; OPERACIONES QUIRURGICAS; OPERATION CHIRURGICALE; Organ Size; OXIDORREDUCTASAS; OXYDOREDUCTASE; pyruvate dehydrogenase; Pyruvate Dehydrogenase Complex - metabolism; SOBREPESO; SUCRE DU SANG; SURPOIDS; TEJIDOS ANIMALES; TISSU ANIMAL; Triglycerides - blood
• ISSN: 1071-7323; 1550-8528
• DOI: 10.1002/j.1550-8528.1996.tb00244.x

Adrenalectomy (ADX) lowers circulating glucose levels in animal models of non-insulin dependent diabetes (NIDDM) and obesity. To investigate the role of hepatic glucose production (HGP) and tissue glucose oxidation in the improvement in glucose tolerance, hepatocyte gluconeogenesis and the activity of pyruvate dehydrogenase (PDH) were examined in different tissues of gold thioglucose (GTG) obese mice 2 weeks after ADX or sham ADX. GTG-obese mice which had undergone ADX weighed significantly less than their adrenal intact counterparts (GTG ADX: 37.5 +/- 0.7g; GTG: 44.1 +/- 0.4g; p0.05), and demonstrated lower serum glucose (GTG ADX: 22.5 +/- 1.6 mmol/L; GTG: 29.4 +/- 1.9 mmol/L; p0.05) and serum insulin levels (GTG ADX: 76 +/- 10 microunit/mL; GTG: 470 +/- 63 microunit/mL; p0.05). Lactate conversion to glucose by hepatocytes isolated from ADX GTG mice was significantly reduced compared with that of hepatocytes from GTG mice (GTG ADX: 125 +/- 10 nmol glucose/10(6) cells; GTG: 403 +/-65 nmol glucose/10(6) cells; p0.05). ADX also significantly reduced both the glycogen (GTG ADX: 165 +/-27 micromole/liver, GTG: 614 +/- 60 micromole/liver; p0.05) and fatty acid content (GTG ADX: 101 +/- 9 mg fatty acid/g liver; GTG: 404 +/- 40 mg fatty acid/g liver; p0.05) of the liver of GTG-obese mice. ADX of GTG-obese mice reduced PDH activity by varying degrees in all tissues, except quadriceps muscle. These observations are consistent with an ADX induced decrease in hepatic lipid stores removing fatty acid-induced increases in gluconeogenesis and increased peripheral availability of fatty acids inhibiting PDH activity via the glucose/fatty acid cycle. It is also evident that the improvement in glucose tolerance which accompanies ADX of GTG-obese mice is not due to increased PDH activity resulting in enhanced peripheral glucose oxidation