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- How do hepatocyte nuclear transcription factors regulate insulin secretion and
glucose metabolism?
Hepatocyte nuclear transcription factors are expressed not only in the liver but
also in the pancreatic β-cells and urogenital tissues. Hepatocyte nuclear tran-
scription factors include HNF-1α, HNF-1β, and HNF-4α. These proteins regu-
late tissue-specific gene expression and thereby determine growth and
development, as well as facilitate metabolic signaling in these organs. During
embryogenesis, these transcription factors act in concert to promote islet devel-
opment and regulate the expression of insulin gene, and genes-encoding pro-
teins which are linked to insulin secretion.- What are the characteristics of MODY 1?
The clinical features of MODY 1 are similar to that of MODY 3 with onset of
diabetes during or after adolescence and progressive decline in β-cell function.
Similar to patients with MODY 3, approximately one-third of patients with
MODY 1 also require insulin for optimal glycemic control. The characteristic
features of MODY 1 are low serum triglyceride, apolipoproteins AII and CIII,
and lipoprotein (a). These lipid abnormalities occur as a result of decreased
HNF 4α which is expressed in hepatocytes and are involved in regulation of
lipoprotein synthesis in the liver. In addition, both micro- and macrovascular
complications are frequently present in patients with MODY 1.- What are the characteristics of MODY 5?
MODY 5 is a result of mutation of gene-encoding HNF-1β and is character-
istically associated with developmental abnormalities of urogenital tract like
renal cysts, vaginal aplasia, and rudimentary/bicornuate uterus. These abnor-
malities are related to the expression of HNF-1β in urogenital epithelial tis-
sues. In addition, MODY 5 is commonly associated with nondiabetic renal
failure (75 %) due to hypoplastic glomerulocystic kidney disease, oligome-
ganephronia, or renal dysplasia. Diabetes is prevalent in approximately 60 %
of individuals and occurs at an early age. MODY 5 is unique in that it is the
only form of MODY where insulin resistance has been reported along with
β-cell dysfunction.- What is the role of NEUROD1 in MODY 6?
NEUROD1 is a transcription factor which is involved in the regulation of
growth and development of islet and neural tissues (cerebellum, hippocampus,
and inner ear). Homozygous inactivating mutations of genes encoding
NEUROD1 result in permanent neonatal diabetes and cerebellar hypoplasia,
whereas heterozygous mutations result in MODY 6 with subtle or no neuro-
logical abnormalities in these individuals.12 Diabetes in the Young