One of the possible causes of insulin deficiency in diabetes is dedifferentiation of β-cells into immature phenotypes with decreased insulin content or into the polyhormonal cells containing both insulin and glucagon. Polyhormonal cells have been detected in the pancreas in diabetic animal models as well as in humans with type 2 diabetes and longstanding type 1 diabetes, suggesting this phenomenon is a consequence of hyperglycemia. However, there is no information about the presence of polyhormonal cells in opposite metabolic conditions such as hypoglycemia in infants with congenital hyperinsulinism (CHI). We examined pancreatic biopsies from 6 infants with diffuse CHI and 5 infants with focal CHI using double immunofluorescence with antibodies to insulin and glucagon. In focal CHI, we found a significant proportion of α-cells containing glucagon and insulin within the focal lesion and in the rest of the tissue. Similarly, in diffuse CHI, we found the majority of α-cells contained glucagon and insulin in all pancreatic islets. The proportion of insulin and glucagon varied in the polyhormonal cells - from cells with equal expression of these hormones to cells with the prevalence of insulin or glucagon. In one diffuse case and in two focal lesions, we observed polyhormonal cells with significantly decreased glucagon expression and normal insulin expression. Outside the latter focal lesions, cells had normal level of glucagon expression. Our results indicate that polyhormonal cells are not exclusive for diabetes and hyperglycemia. We found polyhormonal cells in the pancreas of infants with CHI under hypoglycemic conditions. We suggest that this indicates high degree of the plasticity of the pancreatic cells. The role of plasticity in infants with CHI is yet to be established.


Y.Krivova: None. A.E.Proshchina: None. D.Gubaeva: None. M.Melikyan: None. D.Otlyga: None.

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