Additive effect of islet amyloid polypeptide (IAPP/amylin) and insulin on 2-deoxyglucose uptake in mouse pancreatic acini
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Japanese researchers have contributed to the development of various areas of pancreatic physiology such as hormonal and neural regulation of pancreatic exocrine secretion, effect of nutrients on the exocrine pancreas, and stimulus-secretion coupling in the exocrine pancreas. Among them, we selected three fruitful areas and reviewed them. These are in vitro experiment with the perfusion of the isolated rat pancreas, research related to the cholecystokinin (CCK)-releasing factor of pancreatic acinar cell origin (monitor peptide), and development and characterization of two genetically diabetic rats: WBN/Kob and OLETF (Otsuka Long-Evans Tokushima fatty) rats. PERFUSION OF ISOLATED PANCREASKanno (1) developed an elegant and fine method of perfusion of the rat isolated pancreas. In his study, the inlet of the vascular perfusion was the superior mesenteric artery, and the outlet was the portal vein. The common duct was constantly flushed. The inlet of perfusion of the common duct was the hepatic end of the duct, and the outlet was the duodenal end. This method was further modified to allow more effective perfusion of the vascuSummary: Exocrine pancreatic physiology has been actively investigated in Japan during the past 30 years. We selected three areas and reviewed them for this article. The selected areas are perfusion of the isolated pancreas, cholecystokinin (CCK)-releasing factor from pancreatic juice (monitor peptide), ~ 265 and genetically diabetic rats. The aim of this article is to present a brief overview of the selected areas of exocrine pancreatic physiology in Japan so that future research can be productively directed. Key Words: Exocrine pancreatic physiologyCholecystokinin-releasing factor-Genetically diabetic rats. lar system and simultaneous measuring of the flow rate of pancreatic juice ( 2 ) . The inlets of vascular perfusion were both the superior mesenteric artery and the celiac artery, whereas the outlet was the portal vein. During part of the experiment, the hepatic end of the common duct was ligated, and the pancreatic juice collected from the duodenal end after cannulation with a stainless steel tube (Fig. 1). By using this system of perfusion of the isolated pancreas, Kanno et al.(3) demonstrated that addition of exogenous insulin to the perfusate potentiates the action of CCK to increase both pancreatic-juice flow and amylase release and that raising the glucose concentration in the perfusate potentiates the CCK-induced exocrine secretary response through an increase in endogenous insulin release (Fig. 2 ) . Kanno et al. wrote many articles on the effects of hormones (3-5) and on other factors (2,619) on stimulus-secretion coupling in the exocrine perfused pancreas. Otsuki et al. (19) isolated and perfused rat pancreas according to the technique of Kanno with slight modifications. They measured not only pancreatic-juice flow and amylase output but also insulin (and glucagon) in the portal effluent. Eventually they studied simultaneously both the exocrine and endocrine responses in perfused i...
Japanese researchers have contributed to the development of various areas of pancreatic physiology such as hormonal and neural regulation of pancreatic exocrine secretion, effect of nutrients on the exocrine pancreas, and stimulus-secretion coupling in the exocrine pancreas. Among them, we selected three fruitful areas and reviewed them. These are in vitro experiment with the perfusion of the isolated rat pancreas, research related to the cholecystokinin (CCK)-releasing factor of pancreatic acinar cell origin (monitor peptide), and development and characterization of two genetically diabetic rats: WBN/Kob and OLETF (Otsuka Long-Evans Tokushima fatty) rats. PERFUSION OF ISOLATED PANCREASKanno (1) developed an elegant and fine method of perfusion of the rat isolated pancreas. In his study, the inlet of the vascular perfusion was the superior mesenteric artery, and the outlet was the portal vein. The common duct was constantly flushed. The inlet of perfusion of the common duct was the hepatic end of the duct, and the outlet was the duodenal end. This method was further modified to allow more effective perfusion of the vascuSummary: Exocrine pancreatic physiology has been actively investigated in Japan during the past 30 years. We selected three areas and reviewed them for this article. The selected areas are perfusion of the isolated pancreas, cholecystokinin (CCK)-releasing factor from pancreatic juice (monitor peptide), ~ 265 and genetically diabetic rats. The aim of this article is to present a brief overview of the selected areas of exocrine pancreatic physiology in Japan so that future research can be productively directed. Key Words: Exocrine pancreatic physiologyCholecystokinin-releasing factor-Genetically diabetic rats. lar system and simultaneous measuring of the flow rate of pancreatic juice ( 2 ) . The inlets of vascular perfusion were both the superior mesenteric artery and the celiac artery, whereas the outlet was the portal vein. During part of the experiment, the hepatic end of the common duct was ligated, and the pancreatic juice collected from the duodenal end after cannulation with a stainless steel tube (Fig. 1). By using this system of perfusion of the isolated pancreas, Kanno et al.(3) demonstrated that addition of exogenous insulin to the perfusate potentiates the action of CCK to increase both pancreatic-juice flow and amylase release and that raising the glucose concentration in the perfusate potentiates the CCK-induced exocrine secretary response through an increase in endogenous insulin release (Fig. 2 ) . Kanno et al. wrote many articles on the effects of hormones (3-5) and on other factors (2,619) on stimulus-secretion coupling in the exocrine perfused pancreas. Otsuki et al. (19) isolated and perfused rat pancreas according to the technique of Kanno with slight modifications. They measured not only pancreatic-juice flow and amylase output but also insulin (and glucagon) in the portal effluent. Eventually they studied simultaneously both the exocrine and endocrine responses in perfused i...
The sections in this article are: Protein Chemistry of Amylin Isolation, Structure, Nomenclature, and Evolutionary Relationships Chemical Synthesis Molecular Structure of Soluble Amylin Amylin as the Monomer of Islet Amyloid Molecular Biology Preproamylin Structure and Chromosomal Location of the Human Amylin Gene A Disease‐Associated Mutation in Human Amylin Biosynthesis and Secretion of Amylin Measurement of Amylin Concentrations Tissue Localization and Content Regulation of Biosynthesis Amylin in Extra‐Islet Tissues Circulating Concentrations and Pancreatic Secretion Effects of Secretion Modulators Amylin Secretion in Humans The Amylin Family: Role in the Regulation of Fuel Metabolism Insulin Resistance In Vivo Actions in Skeletal Muscle Role of Calcitonin Gene‐Related Peptide in Skeletal Muscle Metabolism Actions in the Liver Adipose Tissue Regulation of Pancreatic Function Endocrine Pancreas Exocrine Pancreas Regulation of The Gastrointestinal Tract Effects on Gastric Function Intestinal Function Actions in The Central Nervous System: Modulation of Appetite Actions in The Cardiovascular System Calcitonin Gene‐Related Peptide Adrenomedullin Biological Actions of Adrenomedullin in the Cardiovascular System Vascular Actions of Amylin Renal Function Role of Amylin in the Regulation of Renal Function Adrenomedullin: Roles in Renal Function and Sodium Homeostasis Effects on Calcium Metabolism and Bone Actions of Amylin Other Biological Actions Respiratory System Effects in Endocrine Tissues Other than Pancreas Effects in the Immune System Receptors for Amylin and Related Proteins Receptor Nomenclature Pharmacological and Biochemical Studies Calcitonin Receptors Specific Calcitonin Gene‐Related Peptide Binding Sites that Can Interact with Amylin Amylin Binding to Skeletal Muscle and Liver Biochemical Characterization of Putative Amylin and Calcitonin Gene‐Related Peptide Receptors Disease Associations Insulin‐Dependent Diabetes Mellitus Animal Models of Insulin Resistance, Obesity, and Diabetes Obesity and Non‐Insulin‐Dependent Diabetes Mellitus in Humans Other Diabetic Syndromes Amylin in Endocrine Neoplasms Relationship to Aging Other Diseases Conclusion and Future Prospects
Islet amyloid polypeptide (IAPP) in a 37 amino-acid pancreatic islet polypeptide, displaying about 50% amino-acid homology with neuropeptide calcitonin gene-related peptide (CGRP). IAPP is co-stored with insulin in the beta-cell secretory granules and co-released with insulin upon stimulation. Human IAPP has the ability to precipitate in the shape of amyloid in patients with type II (non-insulin dependent) diabetes but otherwise its functional or pathophysiological role is enigmatic. In the present study 125I-labelled rat IAPP was injected i.v. into female Sprague-Dawley rats and the distribution of the peptide was examined by whole-body autoradiography at intervals from 2 to 30 min after administration. Already after 2 min high radioactivity occurred in the lung parenchyma and in the villi of the small intestinal mucosa. The high radioactivity in these tissues persisted at 10 min but at 30 min the radioactive labelling had decreased to a level only slightly higher than that observed in the blood. A high uptake of radioactivity was also seen in the cortex of the kidney. In other tissues, including the liver, the skeletal muscle, and the exocrine and endocrine pancreas, the radioactivity was low and did not exceed that of the blood. The uptake of 125I-IAPP in the lungs and in the small intestine was inhibited by simultaneous injections of either an excess of unlabelled rat IAPP or unlabelled rat CGRP. This indicates that the labelled structures observed in the lung and the small intestine after injection of 125I-IAPP alone was due to binding to receptors for IAPP or CGRP in these tissues. The accumulation of radioactivity in the kidneys was not affected by pretreatment with high doses of unlabelled IAPP or CGRP. This unspecific uptake of radioactivity may be due to reabsorption of labelled IAPP in the proximal tubuli. Our results indicate the presence of receptors binding IAPP in the lung parenchyma and in the villi of the small intestinal mucosa. This, in turn, may imply prominent biological activities of IAPP at these sites.
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