Zebrafish as a preclinical model for diabetes mellitus and its complications: From monogenic to gestational diabetes and beyond

Table 1 Characteristics of maturity-onset diabetes of the young subtypes 1 to 14

Type of MODY	Mutant gene	Clinical characteristics	Therapeutic method	Ref.
MODY 1	HNF4α mutations	Macrosomia; transient neonatal hypoglycemia; insulin secretory defect in adolescence or early adulthood	Low dose sulfonylurea; diet; insulin	[81-83]
MODY2	GCK gene mutation	Small rise in 2-hour PG level on OGTT; higher glucose threshold; nonprogressive elevated fasting blood glucose	Diet and exercise modification (usually no treatment is needed)	[82,84]
MODY3	HNF1A mutation	Lowered renal threshold for glucosuria; insulin secretory defect in adolescence or early adulthood; rise in 2-hour PG level on OGTT	Sulfonylureas	[83,85,86]
MODY4	Mutation of PDX1	Postpuberty; mild form of diabetes	Insulin; OHAs	[87]
MODY5	HNF1B mutation	Renal disease; genitourinary abnormalities; atrophy of the pancreas; hyperuricemia; gout	Early insulin therapy; OHAs (sulfonylurea or repaglinide)	[13]
MODY6	NEUROD1 mutation	Variable age of onset; different degrees of hyperglycemia	Insulin; OHAs	[88]
MODY7	Mutation of KLF11 gene	Variable age of onset; decreased sensitivity to insulin; mild hyperglycemia	Insulin	[89]
MODY8	Mutation of CEL gene	> 25 years; Impaired pancreatic function	Insulin; OHAs	[90]
MODY9	PAX4 gene mutation	Post-puberty; progressive hyperglycemia; occurrences of ketoacidosis	Diet; insulin; OHAs	[91]
MODY10	INS gene mutation	> 10 years; hyperglycemia; diabetes	Insulin; diet	[92]
MODY11	Mutation of BLK gene	Variable age of onset; hyperglycemia; diabetes	Diet; insulin; OHAs	[93]
MODY12	Mutation of ABCC8 gene	Variable age of onset: Diabetes; rarely developmental delay	Sulfonylureas	[94]
MODY13	Gene mutation in member 11 of the inward rectifying potassium ion channel subfamily J (KCNJ11)	After second decade of life; diabetes; possible developmental delay and seizures	Low dose sulfonylures	[95-97]
MODY14	Heterozygous mutation in the APPL1 gene on chromosome 3p14	10-50 years; hyperglycemia; diabetes	Diet; insulin; OHAs	[98]

PG: Plasma glucose; OGTT: Oral glucose tolerance test; OHAs: Oral hypoglycemic agents; MODY: Maturity-onset diabetes of the young; GCK: Glucokinase; HNF1A: Hepatocyte nuclear factor 1A; PDX1: Mutation of pancreatic and duodenal homeobox; NEUROD1: Neurogenic differentiation factor 1; KLF11: Krüppel like factor 11; CEL: Carboxyl ester lipase; PAX4: Paired box gene 4; BLK: B lymphocyte kinase; ABCC8: ATP-binding cassette subfamily C member 8.