She is doing all she
can. Is GIP
the missing link?

GIP: An Incretin Hormone with Diverse Metabolic Roles

GIP is 1 of 2 hormones involved in the incretin effect¹

Both GIP and GLP-1 are hormones secreted by the gut in response to nutrient load. They are responsible for the incretin effect, which enhances the secretion of insulin after a meal.¹

GIP and GLP-1: similarities and differences

GIP has other functions as well. The latest research has shown that GIP may impact weight-related mechanisms, such as food intake and appetite.^1-3 Additionally, several genetic association studies link GIP to the regulation of insulin, glucose, lipids, and body weight.^4-7

Brain

GIP Activity

Reduced food intake*

GLP-1 Activity

Reduced food intake

Increased satiety

Subcutaneous White Adipose Tissue

GIP Activity

Increased insulin sensitivity*

Increased lipid buffering capacity*

Increased storage capacity*

Pancreas

GIP Activity

Increased insulin

Increased glucagon

GLP-1 Activity

Increased insulin

Reduced glucagon

Stomach

GLP-1 Activity

Reduced gastric emptying

^*Derived from preclinical studies; Selected information derived from: Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):416.

The incretin effect is diminished in T2D¹

Over time, hyperglycemia is associated with nephropathy, retinopathy, and CV disease.⁸

WATCH THIS VIDEO TO LEARN MORE ABOUT THE ROLE OF GIP IN T2D

0:09
Following the ingestion of food, cells in the gut release hormones called incretins, which circulate throughout the body to regulate glucose and calorie uptake.

0:19
2 incretins are involved in this process.

0:22
Glucose dependent insulinotropic polypeptide or GIP and Glucagon like peptide one or GLP-1.

0:30
GIP and GLP-1 bind to their respective receptors on pancreatic beta cells resulting in glucose dependent enhancement of insulin secretion.

0:40
Although both incretins are important for optimal postprandial insulin release, evidence suggests that endogenous GIP generates more of an effect on insulin mediated glucose clearance compared with endogenous GLP-1.

0:57
Outside of the pancreas, GIP and GLP-1 may also stimulate other tissues to influence food intake.

1:06
Certain areas of the brain have neuronal cells that express GIP and GLP-1 receptors.

1:14
Activation of certain neuronal cells by GIP and GLP-1 is associated with reduced food intake and body weight regulation.

1:22
Adipocytes express the GIP receptor but not the GLP-1 receptor.

1:28
Stimulation of adipocytes by GIP may promote healthy triglyceride and free fatty acid storage and glucose uptake, improving overall nutrient homeostasis.

1:40
Therefore, growing evidence suggests a key role for incretins in managing nutrient homeostasis and body weight.

1:52
People with type 2 diabetes have diminished insulinotropic responses to both GIP and GLP-1.

2:00
Loss of GIP and GLP-1 signalling results in the inability to properly regulate postprandial glucose levels.

2:09
Decreased beta cell function may contribute to the impaired incretin effect, although the underlying mechanism remains unclear.

2:23
As we learn more about the roles of incretins in regulating glucose and body weight, it is clear that incretins play an even greater role than previously understood in the pathophysiology of type 2 diabetes.

Discover the significant role GIP
plays in regulating blood glucose.

CV=cardiovascular; GIP=glucose-dependent insulinotropic polypeptide; GLP-1=glucagon-like peptide-1; T2D=type 2 diabetes.

References

Nauck MA, Meier JJ. The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol. 2016;4(6):525-536. doi:10.1016/S2213-8587(15)00482-9
Nauck MA, Meier JJ. Incretin hormones: Their role in health and disease. Diabetes Obes Metab. 2018 Feb;20 Suppl 1:5-21. DeFronzo, R.A. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 53, 1270-1287 (2010).
Finan B, Müller TD, Clemmensen C, et al. Reappraisal of GIP pharmacology for metabolic diseases. Trends Mol Med. 2016;22(5):359-376. doi:10.1016/j.molmed.2016.03.005
Saxena R, Hivert MF, Langenberg C, et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010;42(2):142-148. doi:10.1038/ng.521
Speliotes EK, Willer CH, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42(11):937-948. doi:10.1038/ng.686
Karhunen V, Daghlas I, Zuber V, et al. Leveraging human genetic data to investigate the cardiometabolic effects of glucose-dependent insulinotropic polypeptide signalling. Diabetologia. Published online September 9, 2021. doi:10.1007/s00125-021-05564-7
Bowker N, Hansford R, Burgess S, et al. Genetically predicted glucose-dependent insulinotropic polypeptide (GIP) levels and cardiovascular disease risk are driven by distinct causal variants in the GIPR region. Diabetes. 2021;70(11):2706-2719. doi:10.2337/db21-0103
American Diabetes Association. Standards of medical care in diabetes-2021. Diabetes Care. 2021;44(suppl 1):S1-S232

She is doing all she can. Is GIP the missing link?

GIP: An Incretin Hormone with Diverse Metabolic Roles

GIP is 1 of 2 hormones involved in the incretin effect1

GIP and GLP-1: similarities and differences

The incretin effect is diminished in T2D1

WATCH THIS VIDEO TO LEARN MORE ABOUT THE ROLE OF GIP IN T2D

Discover the significant role GIP plays in regulating blood glucose.Learn More

She is doing all she
can. Is GIP
the missing link?

GIP is 1 of 2 hormones involved in the incretin effect¹

The incretin effect is diminished in T2D¹

Discover the significant role GIP
plays in regulating blood glucose.