title: Good glycaemic control reduces oxidation and glycation end-products in collagen of diabetic rats.
abstract: Blood glucose control plays a prominent role in the aetiology of diabetic complications. Recent data support the hypothesis that non-enzymatic pathways (glycation and oxidation) are involved in the pathogenesis of tissue damage in diabetes mellitus. In this study the level of pentosidine, a marker of glycation, and the intensity of collagen-linked fluorescence glycation (370/440 and 335/385 nm) and oxidation-related (356/460 and 390/460 nm), have been examined in spontaneously diabetic rats with good and poor glycaemic control. Pentosidine increased dramatically in rats with poor control, and slightly in those with good control. At the end of the study, after 6 months of diabetes, pentosidine levels were 13 +/- 5 and 2.1 +/- 0.5 pmol/mg collagen, respectively (control rats: 1.1 +/- 0.1 pmol/mg collagen). A similar pattern was observed for both glycation or oxidation-related fluorescence. The group of rats with poor control always showed elevated average values when compared to rats with good control, with a relative increase of over 200%. The results emphasize the role of good glycaemic control in preventing the growth of glycation or oxidation end-products in collagen. On comparison between the general mean level of all glycated haemoglobin and the mean pentosidine level of the three groups, a very good exponential correlation was found (r = 0.993, p < 0.001). The fluorescence values presented a less strong relationship, but a correlation with glycaemic control was still present. If the post-translational modifications of proteins play a leading role in the pathogenesis of complications it is possible to conclude that strict glycaemic control, obtained by accurate insulin therapy can prevent them by inhibiting the non-enzymatic modification of proteins and delaying their accumulation in collagen. The therapeutic implications are obvious.
authors.affiliation: Department of Internal Medicine (DI.M.I.), University of Genoa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Odetti
authors.forename: N
authors.initials: N
authors.lastname: Traverso
authors.forename: L
authors.initials: L
authors.lastname: Cosso
authors.forename: G
authors.initials: G
authors.lastname: Noberasco
authors.forename: M A
authors.initials: MA
authors.lastname: Pronzato
authors.forename: U M
authors.initials: UM
authors.lastname: Marinari
mesh_terms: D000005:Abdomen / Q000033:anatomy & histology / Q000601:surgery; D000375:Aging / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000032:analysis*; D006031:Glycosylation; D006909:Hydroxyproline / Q000032:analysis*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis; D008297:Male; D010084:Oxidation-Reduction; D011897:Random Allocation; D051381:Rats; D011913:Rats, Inbred BB; D013050:Spectrometry, Fluorescence
chemical_list: D001120:Arginine; D001786:Blood Glucose; D003094:Collagen; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006909:Hydroxyproline; D007004:Hypoglycemic Agents; D007328:Insulin; D008239:Lysine; C062187:pentosidine