Basal insulin gene expression significantly improves conventional insulin therapy in type 1 diabetic rats

Hengjiang Dong, Jennifer Altomonte, Nuria Morral, Marcia Meseck, Swan N. Thung, Savio L.C. Woo

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Although a conventional insulin regimen for type 1 diabetes with twice-daily insulin injections is effective in preventing postprandial blood glucose excursions, this treatment is limited by its inadequate control of fasting hyperglycemia. Alternatively, sustained basal hepatic insulin gene expression has been shown to result in fasting normoglycemia in type 1 diabetic rats, although the treated animals still exhibited moderate postprandial hyperglycemia. To test the hypothesis that basal hepatic insulin production can be used as an auxiliary treatment to conventional insulin therapy for achieving better glycemic control, streptozotocin-induced diabetic rats were treated with twice-daily insulin injections, basal hepatic insulin production, or both in combination. Diabetic rats treated by conventional insulin therapy still suffered from fasting hyper-glycemia, but when complemented with basal hepatic insulin production, near-normoglycemia under both fed and fasting conditions was achieved without fasting hypoglycemia. In addition, the combination-treated animals showed significantly enhanced glucose tolerance and markedly improved profiles in lipid metabolism. Furthermore, the combination treatment reduced the elevated fructosamine, glycated hemoglobin, and advanced glycation end products concentrations to normal. These results provide a proof of concept for basal hepatic insulin production as an adjuvant treatment to conventional insulin therapy in type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)130-138
Number of pages9
JournalDiabetes
Volume51
Issue number1
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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