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Urocortin 2 gene transfer reduces fasting glucose, polydipsia, hyperphagia and increases body weight in type 1 diabetes
Author(s) -
Bhargava Raag,
Tay May Ling,
Gao Meihua,
Hammond HK
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.603.8
Subject(s) - urocortin , medicine , endocrinology , saline , insulin , type 2 diabetes , diabetes mellitus , chemistry , receptor
We previously have shown that a single intravenous (IV) injection of Adeno‐associated Virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal and insulin sensitivity in insulin resistant mice (type‐2 diabetes). The current study tests the hypothesis that UCn2 gene transfer is effective in type‐1 diabetes. We used insulin‐deficient Akita mice and assessed water and food consumption, body weight and fasting glucose before and after UCn2 gene transfer. Akita mice (n=50; 21.3±1.5 g; 2.4±0.2 months of age) were used. Sixteen mice with a mean pre‐treatment 12‐hr fasting glucose of 322±80 mg/dL, received either AAV8.UCn2 (5×10 11 genome copies, gc, IV; n=8) or Saline (IV; n=8). Fasting glucose was repeated 8 weeks after gene transfer. Thirty‐four additional mice were used to assess water and food intake and body weight before and 8w after UCn2 gene transfer (5×10 11 gc, IV; n=17) or Saline (IV; n=17). Fasting glucose Before randomization, 12‐hour fasting glucose was similar (Saline: 354±60 mg/dL, n=8; UCn2: 289±88 mg/dL, n=8; p=.11). Eight weeks after treatment, mice that received UCn2 gene transfer showed lower fasting glucose (Saline: 272±69 mg/dL, n=8; UCn2: 106±33 mg/dL, n=8; p<.0001). Water/food intake and body weight Water intake over the 8w course of the study was reduced after UCn2 gene transfer (Saline: 1.15±0.09 ml/day/g; UCn2: 0.63±0.05 ml/day/g; p<.0001) (Fig 1). Food intake over 8w was also reduced by UCn2 gene transfer (Saline: 0.32±0.04 g/day/g; UCn2: 0.22±0.02 g/day/g; p<.0001) (Fig 1). Body weight increased 8w after UCn2 gene transfer (Saline: 24.1±1.0 g; UCn2: 27.8±0.7 g; 2‐way ANOVA p<.0001) (Fig 2). Conclusion UCn2 gene transfer reduces fasting blood glucose and reduces food and water intake. Despite reduced food intake, Akita mice that received UCn2 gene transfer showed increased body weight. These data suggest a possible non‐insulin therapy for type‐1 diabetes. Support or Funding Information I01 BX003774 VA Merit Grant; R42HL122038 NHLBI This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .