Short-term insulin treatment prevents the diabetogenic action of streptozotocin in rats. 1997

J Thulesen, and C Orskov, and J J Holst, and S S Poulsen
University of Copenhagen, Panum Institute, Denmark. J.Thulesen@mai.ku.dk

Streptozotocin, which induces diabetes mellitus in experimental animals, has been reported to be taken up by beta-cells by means of the glucose transporter 2 (GLUT2) and then reduce the cellular level of NAD+, leading to necrosis of the beta-cells. We investigated the effect of insulin pretreatment on the diabetogenic action of streptozotocin (60 mg/kg). Four groups of rats were studied: 1) a group that received streptozotocin (STZ), 2) a group that received insulin pretreatment and streptozotocin (INS + STZ), 3) a group that received insulin (INS), and 4) a control group (CTRL). Insulin treatment reduced the beta-cell immunoreactivity (IR) of insulin and GLUT2, which, thus, was reduced in INS + STZ rats at the time of streptozotocin injection. In STZ rats, plasma insulin concentrations after 3 weeks as well as insulin concentrations in pancreatic tissue samples were significantly lower than those in CTRL rats [plasma, 274.3 +/- 101.9 vs. 1078.8 +/- 254.9 pmol/liter (P < 0.05); tissue, 0.46 +/- 0.02 vs. 117.0 +/- 28.4 nmol/g (P < 0.01)]. INS + STZ rats did not become hyperglycemic, and the plasma and tissue levels of insulin were higher than those in STZ rats [plasma, 538.3 +/- 80.1 vs. 274.3 +/- 101.9 pmol/liter (P = 0.08); tissue, 0.46 +/- 0.02 vs. 37.90 +/- 2.13 nmol/g (P < 0.05)]. The immunohistochemical findings of insulin IR in the pancreatic tissues were in accordance with the results obtained by RIA. We conclude that exogenous insulin suppresses the expression of GLUT2 and insulin in beta-cells, and this may prevent the diabetogenic effect of streptozotocin.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D009004 Monosaccharide Transport Proteins A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES. Hexose Transport Proteins,Band 4.5 Preactin,Erythrocyte Band 4.5 Protein,Glucose Transport-Inducing Protein,Hexose Transporter,4.5 Preactin, Band,Glucose Transport Inducing Protein,Preactin, Band 4.5,Proteins, Monosaccharide Transport,Transport Proteins, Hexose,Transport Proteins, Monosaccharide,Transport-Inducing Protein, Glucose
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D005260 Female Females
D005934 Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511) Glucagon (1-29),Glukagon,HG-Factor,Hyperglycemic-Glycogenolytic Factor,Proglucagon (33-61),HG Factor,Hyperglycemic Glycogenolytic Factor
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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