title: Basal insulin gene expression significantly improves conventional insulin therapy in type 1 diabetic rats.
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 hyperglycemia, 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.
authors.affiliation: Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, New York, USA. dongh01@doc.mssm.edu
authors.forename: Hengjiang
authors.initials: H
authors.lastname: Dong
authors.forename: Jennifer
authors.initials: J
authors.lastname: Altomonte
authors.forename: Nuria
authors.initials: N
authors.lastname: Morral
authors.forename: Marcia
authors.initials: M
authors.lastname: Meseck
authors.forename: Swan N
authors.initials: SN
authors.lastname: Thung
authors.forename: Savio L C
authors.initials: SL
authors.lastname: Woo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D016883:Diabetic Ketoacidosis / Q000517:prevention & control; D015316:Genetic Therapy; D005822:Genetic Vectors; D005951:Glucose Tolerance Test; D007328:Insulin / Q000235:genetics* / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D011923:Rats, Nude; D015996:Survival Rate
chemical_list: D001786:Blood Glucose; D007328:Insulin