title: Streptozotocin causes pancreatic beta cell failure via early and sustained biochemical and cellular alterations.
abstract: The morphological and biochemical changes that occur in the early phase of streptozotocin (STZ)-induced beta cell failure have not been characterized. The pancreas and plasma of rats treated with STZ were processed for morphological and biochemical parameters 1-24 h and 4 weeks after STZ treatment. Marked reduction in body weight was observed as early as 3 h post STZ treatment and hyperglycemia coupled with hypoinsulinaemia appeared in rats 1 h after treatment with STZ. Hyperglycemia, hyperglucagonemia and hypoinsulinemia became permanent 24 h after STZ treatment. The number of insulin-positive cells decreased significantly (p<0.05) at 24 h after STZ treatment with a concomitant increase in the number of glucagon-immunoreactive cells. Electron microscopy showed coalescing of beta cell granules 18 h after STZ treatment. A near to complete degranulation of beta cells settled at 21 h after STZ administration. The pancreatic tissue and plasma levels of adrenaline and noradrenaline increased significantly (p<0.004: pancreatic tissue; p<0.04: plasma) 3 h after STZ treatment and remained high after a reduction at 6 h post STZ treatment. The pancreatic tissue and plasma levels of 5-HIAA decreased significantly (p<0.002 pancreatic tissue; p<0.04: plasma) 1 h after STZ treatment and remained low after a reduction at 6-9 h post STZ treatment. STZ elicited significant dose-dependent increases in insulin secretion from the isolated pancreas. The early changes in catecholamine level may be used in screening and follow-up studies on diabetes mellitus.
authors.affiliation: Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. eadeghate@uaeu.ac.ae
authors.forename: E
authors.initials: E
authors.lastname: Adeghate
authors.forename: R S
authors.initials: RS
authors.lastname: Hameed
authors.forename: A S
authors.initials: AS
authors.lastname: Ponery
authors.forename: S
authors.initials: S
authors.lastname: Tariq
authors.forename: R S
authors.initials: RS
authors.lastname: Sheen
authors.forename: M
authors.initials: M
authors.lastname: Shaffiullah
authors.forename: T
authors.initials: T
authors.lastname: Donáth
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D009994:Osmolar Concentration; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013311:Streptozocin / Q000633:toxicity*; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects
chemical_list: D007328:Insulin; D006897:Hydroxyindoleacetic Acid; D013311:Streptozocin; D005934:Glucagon; D009638:Norepinephrine; D004837:Epinephrine