Interactions of diabetogenic compounds: cyproheptadine and alloxan

Journal Article · Tue Jan 01 04:00:00 EST 1991 · Fundamental and Applied Toxicology; (USA)

DOI:https://doi.org/10.1016/0272-0590(91)90146-U· OSTI ID:5546460

Chatterjee, A K; Varayotha, V; Fischer, L J ^[1]

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1. Michigan State Univ., East Lansing (USA)

Pretreatment with an oral dose (45 mg/kg) of cyproheptadine (CPH), a drug that inhibits secretion and synthesis of insulin. 3 hr before alloxan (100 mg/kg, iv) protects mice from the permanent diabetes produced by alloxan. Pretreated animals at the time of alloxan administration were hyperglycemic. Therefore, the possibility that CPH-induced hyperglycemia protected mice from alloxan was investigated. This was accomplished by giving mannoheptulose (a glucose antagonist) or insulin (to lower blood glucose) after CPH and before alloxan. These interventions eliminated CPH-induced protection from alloxan, indicating a role for CPH-induced hyperglycemia in the protective effect. To confirm that CPH does not protect mice from alloxan-induced diabetes by a direct action, in vitro experiments using isolated pancreatic islets were conducted. Mouse islets were pretreated with CPH, its metabolite desmethylcyproheptadine (DMCPH), or an equal mixture of the two and/or various concentrations of glucose prior to an acute exposure to a toxic concentration of alloxan. Glucose-stimulated insulin release was used as a measure of pancreatic beta-cell function after alloxan exposure. CPH or DMCPH (alone or in combination) pretreatment did not provide protection against alloxan-induced inhibition of insulin release nor did pretreatments potentiate the protective action of glucose against in vitro alloxan toxicity. The results indicate that the protective action of CPH when given to mice before alloxan is due to drug-induced hyperglycemia and not to a direct effect of CPH or its metabolite.

• OSTI ID: 5546460
• Journal Information: Fundamental and Applied Toxicology; (USA), Journal Name: Fundamental and Applied Toxicology; (USA) Vol. 16:1; ISSN FAATD; ISSN 0272-0590
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALLOXAN
ANIMALS
ANTIHISTAMINICS
AZINES
BIOCHEMICAL REACTION KINETICS
BODY
CHEMOTHERAPY
DIABETES MELLITUS
DIGESTIVE SYSTEM
DISEASES
DRUGS
ENDOCRINE DISEASES
ENDOCRINE GLANDS
GLANDS
HETEROCYCLIC COMPOUNDS
HORMONES
HYPERGLYCEMIA
IN VITRO
INSULIN
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
METABOLIC DISEASES
MICE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PANCREAS
PEPTIDE HORMONES
PROTEINS
PYRIMIDINES
REACTION KINETICS
RODENTS
THERAPY
TRACER TECHNIQUES
VERTEBRATES