title: Is Lipotoxicity presents in the early stages of an experimental model of autoimmune diabetes? Further studies in the multiple low dose of streptozotocin model.
abstract: An increased availability of plasma free fatty acids (FFA) seems to play a role in the early stages of experimental type 1 diabetes mellitus induced in C57BL/6J mice by multiple low doses of streptozotoxin (mld-STZ). We analyzed the temporal changes of: (1) plasma and skeletal muscle lipids and their relationship with glucose metabolism; (2) triglyceride (Tg) concentration in isolated islets; (3) intraperitoneal glucose tolerance test; and (4) insulin secretion patterns when the three mutually interactive glucose signaling pathways were activated. Animals were killed by cervical dislocation at days 4, 6, 7, 8, 9 and 12 post first injection of mld-STZ. Compared with control mice, we observed: (1) at day 6, a significant increase of plasma FFA and both muscle and islet Tg content and a significant decrease of muscle pyruvate dehydrogenase activity. These parameters further deteriorated with time. (2) plasma Tg, glucose and insulin levels and glucose tolerance test were significantly different only after day 8. (3) an increase in both phases of the glucose plus palmitate-stimulated insulin secretion was observed at day 4. This effect progressively decreased since day 7 up to day 9. Moreover, an inhibitory action of cerulenin over glucose plus palmitate-stimulated insulin secretion was observed between days 6 and 9. Taken together these results suggest that early alteration in carbohydrate and lipid metabolism could represent a "metabolic window" which would develop between days 6 and 8. Afterwards, subsequent immunological alterations, apoptosis and necrosis induced the destruction of β cells and would mask the results mentioned above.
authors.affiliation: Endocrinology Research Center (CEDIE), Hospital Ricardo Gutierrez, Buenos Aires, Argentina.
authors.forename: Liliana
authors.initials: L
authors.lastname: Karabatas
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Oliva
authors.forename: Eduardo
authors.initials: E
authors.lastname: Dascal
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Hein
authors.forename: Claudia
authors.initials: C
authors.lastname: Pastorale
authors.forename: Adriana
authors.initials: A
authors.lastname: Chicco
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: Lombardo
authors.forename: Juan C
authors.initials: JC
authors.lastname: Basabe
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000473:pathology; D000818:Animals; D015551:Autoimmunity / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced* / Q000150:complications* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004822:Epididymis; D007328:Insulin / Q000097:blood; D052439:Lipid Metabolism Disorders / Q000097:blood / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism; D009929:Organ Size; D013311:Streptozocin / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D007328:Insulin; D013311:Streptozocin