We report a transgenic mouse line in which Akt/protein kinase B (PKB) pathway can be activated in an inducible manner in defined cell types. In this transgenic mouse line, Cre expression allows the expression of a tamoxifen-activatable form of Akt/PKB in a defined cell type. Subsequent injection of tamoxifen triggers the transient activation of Akt/PKB in mice. Thus, this transgenic line allows the transient activation of Akt/PKB pathway in a predefined cell type. We expect that this transgenic system will provide a unique tool to study the roles of Akt/PKB pathway in mice.

Introduction Patients with congenital hyperinsulinism due to ABCC8 variants generally present severe hypoglycaemia and those who do not respond to medical treatment typically undergo pancreatectomy. Few data exist on the natural history of non-pancreatectomised patients. This work aims to describe the genetic characteristics and natural history in a cohort of non-pancreatectomised patients with congenital hyperinsulinism due to variants in the ABCC8 gene. Subjects and Methods Ambispective study of patients with congenital hyperinsulinism with pathogenic or likely pathogenic variants in ABCC8 treated in the last 48 years and who were non-pancreatectomised. Continuous Glucose Monitoring (CGM) has been periodically performed in all patients since 2003. An oral glucose tolerance test (OGTT) was performed if hyperglycemia was detected in the CGM. Results Eighteen non-pancreatectomised patients with ABCC8 variants were included. Seven (38.9%) patients were heterozygous, eight (44.4%) compound heterozygous, two (11.1%) homozygous, and one patient carried two variants with incomplete familial segregation studies. Seventeen patients were followed-up and twelve (70.6%) of them evolved to spontaneous resolution (median age 6.0±4years; range:1-14). Five out of these twelve patients (41.7%) subsequently progressed to diabetes with insufficient insulin secretion. Evolution to diabetes was more frequent in patients with biallelic variants in the ABCC8 gene. Conclusion The high remission rate observed in our cohort makes conservative medical treatment a reliable strategy for the management of patients with congenital hyperinsulinism due to ABCC8 variants. In addition, a periodic follow-up of glucose metabolism after remission is recommended as a significant proportion of patients evolved to impaired glucose tolerance or diabetes (biphasic phenotype).

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