Pancreatic Islet Blood Flow in the Rat After Administration of Islet Amyloid Polypeptide or Calcitonin Gene-Related Peptide ANNIKA M. SVENSSON, STELLAN SANDLER, AND LEIF JANSSON Anesthetized male Sprague-Dawley rats (350-400 g) were injected intravenously with either 0.1,1,15, or 25 nmol rat islet amyloid polypeptide (IAPP), 65 or 650 pmol rat calcitonin gene-related peptide (CGRP), or saline alone. IAPP at the two highest doses decreased the mean arterial blood pressure (BP), increased blood glucose concentrations, and decreased serum insulin concentrations. CGRP at both doses decreased the BP but did not affect the blood glucose concentrations. The blood flow to the whole pancreas, pancreatic islets, adrenal glands, colon, duodenum, liver, and kidney was measured with a microsphere technique 30 min after administration of IAPP and 3 min after injection of CGRP. The two higher doses of IAPP (15 and 25 nmol) markedly reduced the whole pancreatic blood flow, whereas the islet blood flow remained unaffected. This resulted in an increase in the fraction of whole pancreatic blood flow diverted through the islets from - 1 0 to 17%. No blood flow changes in the pancreas or the islets were observed when 0.1 or 1 nmol IAPP was injected. CGRP at both doses caused a decrease in both whole pancreatic and islet blood flow. No changes in fractional islet blood flow were observed, despite similar effects on mean arterial BP as observed after IAPP injections. Neither adrenal, duodenal, colonic, hepatic, skeletal muscle, nor renal blood flow were significantly affected by any of the concentrations of IAPP used, whereas 650 pmol CGRP decreased both duodenal and colonic blood flow. We conclude that IAPP and CGRP have different effects on pancreatic islet blood flow and that IAPP may be of importance for islet blood flow regulation. Diabetes 43:454-58, 1994 From the Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Address correspondence and reprint requests to Dr. Annika M. Svensson, Department of Medical Cell Biology, Biomedical Center, P.O. Box 571, S-751 23, Uppsala, Sweden. Received for publication 30 March 1993 and accepted in revised form 7 October 1993. IAPP, islet amyloid polypeptide; CGRP, calcitonin gene-related peptide; BP, blood pressure. I slet amyloid polypeptide (IAPP) or amylin is a 37- amino acid peptide that forms the major constituent of the amyloid deposits found in islets of most type II diabetic patients (1-3). IAPP is synthesized in the p-cells (2), stored within insulin secretory granules (4), and subsequently released, essentially in concert with insulin (5-8). The physiological effects of IAPP have been suggested to include a receptor-mediated glyco- gen degradation and lactate release from skeletal mus- cle and associated effects on hepatic fuel metabolism, which could counteract hypoglycemic effects induced by insulin (9,10). The possible endocrine and paracrine effects of IAPP on islet hormone secretion remain con- troversial (11,12). However, it has been suggested that IAPP may act on the endocrine pancreas by directly stimulating the islet blood perfusion (13). The rationale for this suggestion was that IAPP may cause a vasodilation (14,15) analogous to that seen after administration of the potent vasodilator calcitonin gene-related peptide (CGRP) (16-18), a neuropeptide that shares an -50% homology with IAPP (1). Because of these putative effects of IAPP on blood perfusion, the aim of this study was to evaluate, with a microsphere technique, whether IAPP affected the blood flow within the pancreas and particularly in the islets. In addition, the specific effect of CGRP on the pancreatic islets was investigated. RESEARCH DESIGN AND METHODS Male Sprague-Dawley rats, weighing 350-400 g, were obtained from a local breeding colony (Biomedical Cen- ter, Uppsala, Sweden) and used in all experiments. The rats had free access to pelleted food (Type R36; AB AnalyCen, Lidkoping, Sweden) and tap water throughout the experiments. Surgical preparation. Rats were anesthetized with an intraperitoneal injection of pentobarbital (50 mg/kg body 454 DIABETES, VOL. 43, MARCH 1994 Downloaded from http://diabetesjournals.org/diabetes/article-pdf/43/3/454/360616/43-3-454.pdf by guest on 04 November 2022