Abstract In this study, we aimed to determine the alter- ations of beta-cell ultrastructure, insulin mRNA and protein products of the same gene on the pancreas of rats following long-term treatment of 5-aminoimidazole-4-carboxamide riboside (AICAR). A single dose of streptozotocin (STZ) 100 mg/kg was injected intraperitoneally (i.p.) to 2-day-old newborn (n2) rats. The rats were divided into three groups. The first group was the n2 STZ-diabetic rats. The second group consisted of n2 STZ-diabetic rats treated with AICAR 10 mg/kg/day for one month. The third group was non-dia- betic control rats. Our findings demonstrate that AICAR treatment decreases the blood glucose level but increases the body weight in n2 STZ-diabetic rats. In the AICAR-treated group, numerous beta cells showed increased insulin gene expression. We also observed increased exocytosis in this group, in an ultrastructural manner. As a result, it is sug- gested that AICAR may induce insulin synthesis and beta- cell regeneration in n2 STZ-diabetic rats. Key words Neonatal diabetes • AICAR • Beta-cell • Rat Introduction AMP-activated protein kinase (AMPK) activation in beta cells is induced by the adenosine analogue, AICAR, which is phosphorylated to form ZMP, an analogue of 5’-AMP [1–5]. AICAR is likely to mimic many of the physiologi- cal effects of AMP. AICAR has been reported to exert var- ious effects in several types of eukaryotic cells [6–10]. In rodents, STZ is a beta-cell toxin that can produce diabetes mellitus. The neonatal STZ models are appropriate for investigations in diabetes pharmacotherapy [11]. Some investigators reported that AICAR may exert both a posi- tive and negative insulinotropic action in non-insulin- dependent diabetes mellitus (NIDDM) [12–15]. Therefore, we aimed to investigate the effects of AICAR treatment on the beta cell and insulin gene expression in neonatal STZ-diabetic rats. Materials and methods Experimental design and treatment of animals The principles of laboratory animal care (NIH publication no. 83–25, revised 1985) and national laws on animal use were observed in the present study, which was authorised by the Ethical Committee for Animal Research of the Cerrahpasa Faculty of Medicine, Istanbul University, Turkey. In this study, Wistar albino newborn rats from DETAE (Istanbul University Institute of Experimental Medical Research and Application) were used. The animals were fed with pellet chow and tap water ad libitum. A single dose of 100 mg/kg STZ (Sigma) was inject- ed i.p. to 2-day-old newborn rats to induce neonatal STZ dia- betes (n2-STZ). STZ was freshly prepared in 0.25 ml of saline buffer. The animals were randomly divided into three groups. The first group was the n2 STZ-diabetic rats (n=6), sacrificed at the end of the 16th week. The second group consisted of n2 STZ- diabetic rats (n=5) treated with AICAR 10 mg/kg/day for one Acta Diabetol (2006) 43:61–65 DOI 10.1007/s00592-006-0214-6 M. Ozturk • S. Bolkent • F. Kaya-Dagistanli • M. Tuncdemir • S. Yilmazer • A.G. Akkan The effects of 5-aminoimidazole-4-carboxamide riboside on the pancreas in neonatal streptozotocin-diabetic rats ORIGINAL M. Ozturk • S. Bolkent () • F. Kaya-Dagistanli M. Tuncdemir • S. Yilmazer Department of Medical Biology Cerrahpasa Faculty of Medicine Istanbul University Cerrahpasa, Istanbul, Turkey E-mail: bolkent@istanbul.edu.tr A.G. Akkan Department of Pharmacology Cerrahpasa Faculty of Medicine Istanbul University Cerrahpasa, Istanbul, Turkey Received: 25 January 2005 / Accepted in revised form: 25 May 2006