MODY 1 is a form of
maturity onset diabetes of the young
Maturity-onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. MODY is often referred to as monogenic diabetes to disting ...
.
MODY 1 is due to a loss-of-function mutation in the ''
HNF4A
Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 (nuclear receptor subfamily 2, group A, member 1) is a nuclear receptor that in humans is encoded by the ''HNF4A'' gene.
Function
HNF-4α is a nuclear transcription factor that bind ...
'' (''MODY1'') gene on
chromosome 12. This gene codes for hepatocyte nuclear factor 4-alpha (HNF4-α) protein also known as
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
14 (TCF14).
HNF4α controls function of
HNF1α (see
MODY 3
MODY 3 (also HNF1A-MODY) is a form of maturity-onset diabetes of the young. It is caused by mutations of the HNF1-alpha gene, a homeobox gene on human chromosome 12. This is the most common type of MODY in populations with European ancestry, acco ...
; ) and perhaps
HNF1β (
MODY 5
Renal cysts and diabetes syndrome (RCAD), also known as MODY 5, is a form of maturity onset diabetes of the young.
Presentation
HNF1β-related MODY is one of the less common forms of MODY, with some distinctive clinical features, including atroph ...
) as well. This transcription network plays a role in the early development of the
pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an ...
,
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
, and
intestine
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans an ...
s. In the pancreas these genes influence expression of, among others, the genes for insulin, the principal
glucose transporter (
GLUT2
Glucose transporter 2 (GLUT2) also known as solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2) is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the princ ...
), and several proteins involved in glucose and mitochondrial metabolism.
Although pancreatic beta cells produce adequate insulin in infancy, the capacity for insulin production declines thereafter. Diabetes (persistent hyperglycemia) typically develops by early adult years, but may not appear until later decades. The degree of insulin deficiency is slowly progressive. Many patients with MODY 1 are treated with
sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the bet ...
s for years before insulin is required.
Liver effects are subtle and not clinically significant. Many people with this condition have low levels of
triglyceride
A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride'').
Triglycerides are the main constituents of body fat in humans and other vertebrates, as ...
s,
lipoprotein(a),
apolipoproteins
AII and
CIII
CIII-DT (channel 41) is a television station in Toronto, Ontario, Canada, serving as the flagship station of the Global Television Network. Owned and operated by network parent Corus Entertainment, CIII-DT maintains studios at 81 Barber Gree ...
.
References
External links
Diabetes
{{endocrine-disease-stub