Neonatal Diabetes

DefiniGEN provide disease modelled neonatal diabetes human pancreatic cells which are highly functional CRISPR gene-edited human pancreatic cells. Neonatal diabetes mellitus (NDM) is a rare but potentially devastating metabolic disorder characterized by hyperglycemia combined with low levels of insulin. The neonatal diabetes cell products display the disease phenotype in combination with general function comparable to human primary pancreatic islets. These cell products can offer disease modelling and drug discovery researchers unprecedented tool for elucidating the underlying mechanisms of this key form of monogenic diabetes.

• Highly standardized cell product containing >97% human pancreatic cells with consistent performance and biologically relevant data
• Disease circuit verified confirmed mutation in KCNJ11 gene encoding Kir6.2 subunit of potassium channels – CAT>CGT at codon 201
• Phenotypic analysis of the cells using GSIS assays demonstrates that the insulin response to glucose challenge is dysfunctional in these disease modelled cell products in contrast to DefiniGEN’s isogenic wild-type control pancreatic cell products.

Pancreatic Cell Morphology

Def-PANC WT cells and Neonatal disease model variants display typical pancreatic cell morphology.

Figure 1. Morphology of Def-PANC Neonatal KCNJ11 heterozygous mutated cells on the day of cryopreservation. Magnification: 100x Disease Circuit Verification

Disease Circuit Verification

Neonatal Diabetes disease model with confirmed mutation in KCNJ11 gene encoding Kir6.2 subunit of potassium channels – CAT>CGT at codon 201 – isogenic control available

Figure 2. Sanger sequencing of Def-PANC NDM. Sequence shows heterozygous KCNJ11 mutation with single base change (CAT>CGT) at codon 201 in the gene encoding for the ATP-sensitive potassium channel subunit Kir6.2.

Glucose Stimulated Insulin Secretion Assay

Def-PANC Neonatal diseased modelled cell products display dysfunctional GSIS results in contrast to wild-type Def-PANC cells which exhibit an effective GSIS response.

Figure 3. GSIS response in Def-PANC NDM and in gene control. Def-PANC WT isogenic controls shows expected glucose cycling GSIS response at low and high glucose concentrations. The Def-PANC Neonatal disease model shows dysfunction in its glucose responsive insulin production in contrast to the isogenic WT control. Genetic information and phenotypic response confirm that Def-PANC NDM cells are an effective model of neonatal diabetes.