Ins1, or insulin 1, is one of the two genes coding for insulin in rats, located on chromosome 1 [2,3]. Insulin is crucial for maintaining glucose homeostasis as it stimulates glucose uptake by peripheral tissues, thus pancreatic beta cells, which secrete insulin, play a central role in this process. Genetic models, such as KO/CKO mouse models, are valuable tools for studying Ins1's function and its impact on whole-body glucose homeostasis.

Several Ins1-related mouse models have been developed. Ins1(Cre) and Ins1(CreERT2) mice allow for efficient and selective recombination of floxed genes in beta cells from birth or upon tamoxifen treatment in adults respectively, with no recombination in the central nervous system [1]. Generation of Ins1-cre-driver C57BL/6N mice and C57BL/6J-Ins1(em1 (cre) Utr) mice also enables pancreatic beta-cell-specific Cre-loxP recombination [4,6]. Moreover, in Ins2-/-mutants, there is a dramatic increase in Ins1 transcripts, along with beta-cell hyperplasia, compensating for the low insulin production [5].

In conclusion, Ins1 is essential for insulin production and glucose homeostasis. Studies using Ins1-related KO/CKO mouse models have revealed its role in pancreatic beta-cell function and compensatory responses in the context of insulin deficiency. These models contribute significantly to understanding the pathophysiology of diabetes and related metabolic disorders [1,4,5,6].

References:

1. Thorens, Bernard, Tarussio, David, Maestro, Miguel Angel, Heikkilä, Eija, Ferrer, Jorge. 2014. Ins1(Cre) knock-in mice for beta cell-specific gene recombination. In Diabetologia, 58, 558-65. doi:10.1007/s00125-014-3468-5. https://pubmed.ncbi.nlm.nih.gov/25500700/

2. Kiba, T. . OVEREXPRESSION OF PDX-1 GENE INCREASES INS1 GENE mRNA EXPRESSION, NOT INS2 GENE mRNA EXPRESSION, IN INSULINOMA CELL LINE RIN-5F. In Acta endocrinologica (Bucharest, Romania : 2005), 18, 164-167. doi:10.4183/aeb.2022.164. https://pubmed.ncbi.nlm.nih.gov/36212267/

3. Kiba, T. 2024. OVEREXPRESSION OF PTEN GENE INCREASES INS2 GENE MRNA EXPRESSION, NOT INS1 GENE MRNA EXPRESSION, IN INSULINOMA CELL LINE RIN-5F. In Acta endocrinologica (Bucharest, Romania : 2005), 19, 277-280. doi:10.4183/aeb.2023.277. https://pubmed.ncbi.nlm.nih.gov/38356984/

4. Hasegawa, Yoshikazu, Daitoku, Yoko, Mizuno, Seiya, Sugiyama, Fumihiro, Yagami, Ken-ichi. . Generation and characterization of Ins1-cre-driver C57BL/6N for exclusive pancreatic beta cell-specific Cre-loxP recombination. In Experimental animals, 63, 183-91. doi:. https://pubmed.ncbi.nlm.nih.gov/24770644/

5. Leroux, L, Desbois, P, Lamotte, L, Bucchini, D, Joshi, R L. . Compensatory responses in mice carrying a null mutation for Ins1 or Ins2. In Diabetes, 50 Suppl 1, S150-3. doi:. https://pubmed.ncbi.nlm.nih.gov/11272179/

6. Hasegawa, Yoshikazu, Hoshino, Yoshikazu, Ibrahim, Abdelaziz E, Mizuno, Seiya, Sugiyama, Fumihiro. 2016. Generation of Nuclease technology-mediated bicistronic knock-in ins1-cre driver mice. In Experimental animals, 65, 319-27. doi:10.1538/expanim.16-0016. https://pubmed.ncbi.nlm.nih.gov/27053096/