Characterization of streptozotocin-induced diabetic rats and pharmacodynamics of insulin formulations

Morphological and functional changes of rat pancreatic islets caused by administration of streptozotocin (STZ) and the bioavailability of insulin formulations administered to STZ-induced diabetic rats with fasting (12 h) or non-fasting were investigated. Islets isolated from normal rats maintained a...

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Veröffentlicht in:Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2003-11, Vol.67 (11), p.2396-2401
Hauptverfasser: Lee, J.J. (Korea Univ., Seoul (Korea R.)), Yi, H.Y, Yang, J.W, Shin, J.S, Kwon, J.H, Kim, C.W
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container_issue 11
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container_title Bioscience, biotechnology, and biochemistry
container_volume 67
creator Lee, J.J. (Korea Univ., Seoul (Korea R.))
Yi, H.Y
Yang, J.W
Shin, J.S
Kwon, J.H
Kim, C.W
description Morphological and functional changes of rat pancreatic islets caused by administration of streptozotocin (STZ) and the bioavailability of insulin formulations administered to STZ-induced diabetic rats with fasting (12 h) or non-fasting were investigated. Islets isolated from normal rats maintained a good three-dimensional structure and the islet yield was 962.5 =+- 86.5 islet equivalent number (IEQ, islets converted to an average diameter of 150 micro m). In the diabetic group (>500 mg/ ml blood glucose), the islet yield was only 44.4 =+- 8.3 IEQ and the islet was severely damaged. The minimum reduction of blood glucose of each formulation, such as insulin solution, microcrystal, and insulin microcrystal capsule, was shown to be 11.3, 11.0, and 16.3 mg/dl, respectively, at 6 h in fasting with diabetic rats. These results indicated that the administration of insulin formulations to the fasting groups increased the severe hypoglycemic effect of insulin action more than in non-fasting diabetic rats. The diabetic rat with fasting has a regulatory disorder in maintaining the blood glucose level. Accordingly, the validity of pharmacological availability as an optimal modeling of insulin formulations is best in non-fasting STZ-induced diabetic rats.
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The minimum reduction of blood glucose of each formulation, such as insulin solution, microcrystal, and insulin microcrystal capsule, was shown to be 11.3, 11.0, and 16.3 mg/dl, respectively, at 6 h in fasting with diabetic rats. These results indicated that the administration of insulin formulations to the fasting groups increased the severe hypoglycemic effect of insulin action more than in non-fasting diabetic rats. The diabetic rat with fasting has a regulatory disorder in maintaining the blood glucose level. 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In the diabetic group (&gt;500 mg/ ml blood glucose), the islet yield was only 44.4 =+- 8.3 IEQ and the islet was severely damaged. The minimum reduction of blood glucose of each formulation, such as insulin solution, microcrystal, and insulin microcrystal capsule, was shown to be 11.3, 11.0, and 16.3 mg/dl, respectively, at 6 h in fasting with diabetic rats. These results indicated that the administration of insulin formulations to the fasting groups increased the severe hypoglycemic effect of insulin action more than in non-fasting diabetic rats. The diabetic rat with fasting has a regulatory disorder in maintaining the blood glucose level. 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Psychology</subject><subject>Glucose Tolerance Test</subject><subject>Hypoglycemic Agents - pharmacokinetics</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>INSULIN</subject><subject>Insulin - pharmacokinetics</subject><subject>Insulin - therapeutic use</subject><subject>islet</subject><subject>Islets of Langerhans - pathology</subject><subject>Islets of Langerhans - secretion</subject><subject>Kinetics</subject><subject>Male</subject><subject>MANKIND</subject><subject>Pancreas - pathology</subject><subject>pharmacodynamics</subject><subject>PHARMACOLOGY</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>streptozotocin</subject><issn>0916-8451</issn><issn>1347-6947</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0M1rHCEYBnApCc027annloHQXsps1VFnPIYl_QiB9JCc5R11WsOMbtQhbP76ON0tgZKDCvJ7H14ehN4TvCa0JV_7vl-Ldk0bKV6hFWlYWwvJ2iO0wpKIumOcnKA3Kd1hXD44eY1OCBNMEClXyG7-QASdbXSPkF3wVRiqlKPd5vAYctDO186bWVtTGQe9zU5XEXKqwJtqW4Yn0MHsPExOp2XY-TSPzldDiNM8_s1Mb9HxAGOy7w7vKbr9dnGz-VFfXX__uTm_qrUQPNcCc9n1oiVN1zSCakxFK7puoOUi3BjSEYulBN5rwwYjygHBGYVOMip72Zyiz_vcbQz3s01ZTS5pO47gbZiTagmjtCQUePYfvAtz9GU3RRiTjBe0qC97pWNIKdpBbaObIO4UwWrpXpXulWjV0n3RHw-Zcz9Z82wPZRfw6QAgaRiHCF679Ow4w5xiVpzYO-eXEuEhxNGoDLsxxH9DzcsbfNgPDhAU_I7FXf6iGDOMywpd8wStzKfs</recordid><startdate>20031101</startdate><enddate>20031101</enddate><creator>Lee, J.J. 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Psychology</topic><topic>Glucose Tolerance Test</topic><topic>Hypoglycemic Agents - pharmacokinetics</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>INSULIN</topic><topic>Insulin - pharmacokinetics</topic><topic>Insulin - therapeutic use</topic><topic>islet</topic><topic>Islets of Langerhans - pathology</topic><topic>Islets of Langerhans - secretion</topic><topic>Kinetics</topic><topic>Male</topic><topic>MANKIND</topic><topic>Pancreas - pathology</topic><topic>pharmacodynamics</topic><topic>PHARMACOLOGY</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>streptozotocin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, J.J. 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Islets isolated from normal rats maintained a good three-dimensional structure and the islet yield was 962.5 =+- 86.5 islet equivalent number (IEQ, islets converted to an average diameter of 150 micro m). In the diabetic group (&gt;500 mg/ ml blood glucose), the islet yield was only 44.4 =+- 8.3 IEQ and the islet was severely damaged. The minimum reduction of blood glucose of each formulation, such as insulin solution, microcrystal, and insulin microcrystal capsule, was shown to be 11.3, 11.0, and 16.3 mg/dl, respectively, at 6 h in fasting with diabetic rats. These results indicated that the administration of insulin formulations to the fasting groups increased the severe hypoglycemic effect of insulin action more than in non-fasting diabetic rats. The diabetic rat with fasting has a regulatory disorder in maintaining the blood glucose level. Accordingly, the validity of pharmacological availability as an optimal modeling of insulin formulations is best in non-fasting STZ-induced diabetic rats.</abstract><cop>Tokyo</cop><pub>Japan Society for Bioscience, Biotechnology, and Agrochemistry</pub><pmid>14646199</pmid><doi>10.1271/bbb.67.2396</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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source J-STAGE Free; MEDLINE; Oxford University Press Journals All Titles (1996-Current); Open Access Titles of Japan; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry
subjects Animals
ANTIBIOTICS
Biological and medical sciences
Blood Glucose - drug effects
Blood Glucose - metabolism
Cell Separation
DIABETES
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - pathology
Fundamental and applied biological sciences. Psychology
Glucose Tolerance Test
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - therapeutic use
INSULIN
Insulin - pharmacokinetics
Insulin - therapeutic use
islet
Islets of Langerhans - pathology
Islets of Langerhans - secretion
Kinetics
Male
MANKIND
Pancreas - pathology
pharmacodynamics
PHARMACOLOGY
Rats
Rats, Sprague-Dawley
streptozotocin
title Characterization of streptozotocin-induced diabetic rats and pharmacodynamics of insulin formulations
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