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Am J Physiol Endocrinol Metab (February 19, 2002). doi:10.1152/ajpendo.00564.2001
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Articles in PresS, published online ahead of print February 19, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00564.2001
Submitted on December 21, 2001
Accepted on February 12, 2002

Mild Streptozotocin Diabetes in the Gottingen Minipig. A Novel Model of Moderate Insulin Deficiency and Diabetes

Marianne O Larsen*, Michael Wilken, Carsten F Gotfredsen, Richard D Carr, Ove Svendsen, and Bidda Rolin

* To whom correspondence should be addressed. E-mail: mmla{at}novonordisk.com.

Non-rodent models of diabetes are needed for practical and physiological reasons. Induction of mild insulin deficient diabetes was investigated in male Gottingen minipigs using streptozotocin (STZ) alone (75,100 and 125mg/kg) or 125mg/kg in combination with pretreatment with nicotinamide (NIA)(0,20,67,100,150 and 230mg/kg). Use of NIA resulted in a less steep slope of the regression line between FPG and changing doses compared to STZ(-7.0±1.4 vs. 29.7±7.0mM*(mg*kg-1)-1, p<0.0001). Intermediate NIA doses induced moderate changes of glucose tolerance(AUCglucose increased from 940±175 to 1598±462mM*min, p<0.001(100mg/kg) and from 890±109 to 1669±691mM*min, p=0.003(67mg/kg)) with reduced insulin secretion(1248±602 after 16 and 1566±190 after 60 days vs. 3251±804pM*min in normal animals (p<0.001)) and ß-cell mass(5.5±1.4 after 27 and 7.9±4.1 after 60 days vs. 17.7±4.7mg/kg in normal animals (p=0.009)). The combination of NIA and STZ provided a model characterized by fasting and especially postprandial hyperglycemia, and reduced, but maintained, insulin secretion and ß-cell mass. This model holds promise as an important tool for studying the pathophysiology of diabetes and development of new pharmacological agents for treatment of the disease.




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