title: Effects of long-acting somatostatin analogues on redox systems in rat lens in experimental diabetes.
abstract: The effects of long-acting somatostatin analogues, angiopeptin (AGP) and Sandostatin (SMS), on the early decline in the lens content of glutathione (GSH), ATP and NADPH and increase in sorbitol were studied in STZ diabetic rats, and comparison was made with the effect of insulin. Three factors prompted this study: (i) the known increase in IGF-1 in ocular tissue in diabetes and antagonistic effect of somatostatins, (ii) the known effect of IGF-1 in increasing lens aldose reductase and (iii) the lack of effect of somatostatins on diabetic hyperglycaemia, the latter enabling a differentiation to be made between effects of hyperglycaemia per se and site(s) of IGF-1/somatostatins. All four metabolites studied showed a significant restoration towards the normal control level after 7 days of treatment with AGP and SMS, and AGP was more effective on levels of GSH and ATP. A significant correlation was found between GSH and ATP across all groups at 7 days treatment. The redox state changes in diabetes include both NADP+/NADPH and NAD+/NADH in the conversion of glucose to sorbitol and via sorbitol dehydrogenase to fructose with a linked decrease in ATP formation via NAD+/NADH regulation of the glycolytic pathway. The interlinked network of change includes the requirement for ATP in the synthesis of GSH. The present study points to possible loci of action of somatostatins in improving metabolic parameters in the diabetic rat lens via effects on aldose reductase and/or glucose transport at GLUT 3.
authors.affiliation: Division of Biosciences, Research Department of Cell and Developmental Biology, University College London, London, UK.
authors.forename: Sirilaksana
authors.initials: S
authors.lastname: Kunjara
authors.forename: A Leslie
authors.initials: AL
authors.lastname: Greenbaum
authors.forename: Milena
authors.initials: M
authors.lastname: Sochor
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbaek
authors.forename: Patricia
authors.initials: P
authors.lastname: McLean
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000449:Aldehyde Reductase / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009249:NADP / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010456:Peptides, Cyclic; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D007328:Insulin; D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D009249:NADP; D000255:Adenosine Triphosphate; D000449:Aldehyde Reductase; D005978:Glutathione; D005947:Glucose; D015282:Octreotide
keywords: ATP; angiopeptin; experimental diabetes (STZ); glutathione; insulin; rat lens; redox systems; sandostatin