Insulin degludec and glutamine dipeptide modify glucose homeostasis and liver metabolism in diabetic mice undergoing insulin-induced hypoglycemia (2024)

J Appl Biomed 19:210-219, 2021|DOI:10.32725/jab.2021.025

Insulin degludec and glutamine dipeptide modify glucose homeostasis and liver metabolism in diabetic mice undergoing insulin-induced hypoglycemia

Camila Bataglini¹, Isabela Ramos Mariano², Sílvia Carla Ferreira Azevedo³, Valder Nogueira Freire⁴, Maria Raquel Marçal Natali³, Maria Montserrat Dias Pedrosa², Rosane Marina Peralta¹, Anacharis B. Sá-Nakanishi¹, Lívia Bracht¹, Vilma A. Ferreira Godoy², Adelar Bracht¹, Jurandir Fernando Comar^{1, *}

¹State University of Maringá, Department of Biochemistry, Maringá, PR, Brazil

²State University of Maringá, Department of Physiological Sciences, Maringá, PR, Brazil

³State University of Maringá, Department of Morphological Sciences, Maringá, PR, Brazil

⁴Federal University of Ceará, Department of Physics, Fortaleza, CE, Brazil

This study investigated whether a 30-day co-treatment with 1 g/kg glutamine dipeptide (GdiP) and 1 U/kg regular (rapid acting) or 5 U/kg degludec (long acting) insulins modifies glucose homeostasis and liver metabolism of alloxan-induced type 1 diabetic (T1D) male Swiss mice undergoing insulin-induced hypoglycemia (IIH). Glycemic curves were measured in fasted mice after IIH with 1 U/kg regular insulin. One hour after IIH, the lipid profile and AST and ALT activities were assayed in the serum. Morphometric analysis was assessed in the liver sections stained with hematoxylin-eosin and glycolysis, glycogenolysis, gluconeogenesis and ureagenesis were evaluated in perfused livers. T1D mice receiving GdiP or the insulins had a smaller blood glucose drop at 60 minutes after IIH, which was not sustained during the subsequent period up to 300 minutes. The 30-day treatment of T1D mice with insulin degludec, but not with regular insulin, improved fasting glycemia, body weight gain and serum activity of AST and ALT. Treatments with insulin degludec, GdiP and insulin degludec + GdiP decreased the liver capacity in synthesizing glucose from alanine. GdiP, in combination with both insulins, was associated with increases in the serum triglycerides and, in addition, regular insulin and GdiP increased AST and ALT activities, which could be the consequence of hepatic glycogen overload. GdiP and the insulins improved the IIH, although to a small extent. Caution is recommended, however, with respect to the use of GdiP because of its increasing effects on serum triglycerides and AST plus ALT activities.

Keywords: Gluconeogenesis; Glutamine dipeptide; Insulin degludec; Insulin-induced hypoglycemia; Liver metabolism; Type I diabetes

Grants and funding:

The authors wish to thank CAPES and CNPq for the financial support.

Conflicts of interest:

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) had no involvement in the study design, the collection, analysis and interpretation of data, the writing of the report, nor the decision to submit the article for publication.

Received: December 3, 2020; Revised: September 21, 2021; Accepted: October 21, 2021; Prepublished online: November 2, 2021; Published: December 6, 2021 Show citation

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