How An Insulin Gene Influences Diet and Blood Sugar (GIPR)

The GIPR gene is responsible for encoding a protein with the same name, GIPR (which is short for gastric inhibitory polypeptide receptor) [R].

The GIPR gene and the protein it helps create play an important role in insulin production in the body [R].

Research has found that certain variants in the GIPR gene can alter the body’s ability to secrete insulin. As a result, these variants may be associated with insulin resistance, diabetes, obesity [R, R, R].

The GIPR protein is created from the GIPR gene.

The ‘R’ in GIPR stands for receptor, as it acts as a receptor for the GIP protein [R].

The GIP protein belongs to a class of hormones called incretins, which are responsible for regulating blood sugar (glucose) levels [R].

When glucose levels become high, such as after a meal, GIP is secreted from special intestinal cells called K cells [R].

This newly secreted GIP binds to GIPR located on the pancreas, which causes insulin secretion [R].

Insulin allows the body to use or store glucose, which helps lower blood glucose levels [R].

How Do GIPR Variants Affect Metabolic Health?

Research suggests that certain variants in the GIPR gene may influence aspects of metabolic health, such as insulin resistance, type 2 diabetes, and body fat [R, R].

This is because the primary function of GIPR (along with GIP) is to stimulate the production of insulin in response to a rise in blood sugar (glucose) levels, such as after a meal [R].

Certain GIPR variants can impair this function, leading to reduced secretion of insulin [R].

This reduced ability to produce insulin can hinder the body’s ability to process glucose, which can lead to elevated blood glucose levels. This may lead to metabolic disorders, such as diabetes and obesity [R, R].

Who Is Affected?

There are several specific variants in GIPR that are associated with metabolic disorders. 

In the following sections, we’ll go over each of these variants and highlight which groups of people may be affected.

The rs10423928 Variant

One of the more well-researched SNPs in the GIPR gene is rs10423928.

There are two possible alleles in rs10423928: the more common ‘T’ allele and the less common ‘A’ allele.

Carrying the ‘T’ allele usually results in normal gene function, while the ‘A’ allele is associated with decreased insulin secretion [R].

According to a meta-analysis of 16 studies including over 57,000 patients of European descent, the ‘A’ allele is moderately associated with an increased risk of type 2 diabetes [R].

Similar results were found in a study of over 6,800 individuals from Shanghai, China. The ‘A’ allele was linked to type 2 diabetes susceptibility in this Chinese population [R].

Another study looked at over 5,000 pregnant women from Northern India. Researchers found that the ‘A’ allele was linked to worse insulin resistance and a trend towards gestational diabetes (a type of diabetes that can occur during pregnancy) [R].

The ‘A’ allele is associated with insulin resistance and type 2 diabetes in European and Chinese groups. It has also been linked to gestational diabetes in Indian women.

The rs2302382 Variant

The two alleles in rs2302382 are the more common ‘C’ allele and the rare ‘A’ allele.

There is evidence that the ‘A’ allele in rs2302382 is linked to metabolic disorder, likely due to impaired insulin secretion [R, R].

For example, a study of 300 Egyptian patients suggests that the ‘A’ allele is associated with type 2 diabetes [R].

A study of over 700 German families found that the ‘A’ allele is significantly more common in obese adults and children [R].

However, there is conflicting evidence. Based on a population study of over 4,300 German individuals, the ‘A’ allele was actually linked to lower BMI [R].

In rs2302382, the ‘A’ allele is associated with type 2 diabetes in Egyptian individuals. The ‘A’ allele may also be linked to obesity in German populations, although there is conflicting evidence.

The rs11671664 Variant

The two possible alleles in rs11671664 are the common ‘G’ allele and the much more uncommon ‘A’ allele.

In this case, the more common ‘G’ allele appears to be associated with higher BMI, according to a study of close to 28,000 individuals of East Asian descent [R].

It’s not entirely clear how the ‘G’ allele in this SNP affects the function of the GIPR gene.

The ‘G’ allele in rs11671664 may be associated with higher BMI in East Asians.

You can see your genotypes for GIPR in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations — so you should interpret your results with caution if you are not descended from one of these specific groups!

Primary SNPs: 

GIPR rs10423928

• ‘T’ = Normal metabolic function
• ‘A’ = Associated with insulin resistance, type 2 diabetes, and gestational diabetes
• These associations have only been found in European, Chinese, and Indian populations
• Only about 3% of all people worldwide have the ‘AA’ genotype (highest risk)

GIPR rs2302382

• ‘C’ = Normal metabolic function
• ‘A’ = Associated with insulin resistance, type 2 diabetes, and obesity
• These associations have only been found in Egyptian and German populations
• Only about 4% of all people worldwide have the ‘AA’ genotype (highest risk)

GIPR rs11671664

• ‘A’ = Not associated with metabolic disorder
• ‘G’ = Associated with higher BMI
• This association has only been found in East Asian populations
• About 73% of all people worldwide have the ‘GG’ genotype (highest risk)