The Power Of GIP And GLP-1 Together
Watch Thomas Forst, discuss the potential pleiotropic effects of incretins, including their effects on glycemic control, food intake, and lipid metabolism.
Hello, everyone, ladies and gentlemen, dear colleagues, my name is Thomas Forst, and I will speak now about the role of GIP as one of the incretins in the human body.
Though we talk about incretins, then we talk about two different cell types in the intestine, which are the L-cells and the K-cells, and you see over here in the L-cells, we have glucagon like peptide 1, GLP-1, but from L-cells there are other intestinal hormones which are secreted, which is oxyntomodulin, which is a weak GLP-1 and GIP agonist. Then we have the peptide YY from the L-cells, which is something which plays a role in energy metabolism and appetite regulation. And on the other hand, we have the K-cells, and there we have glucose dependent insulinotropic hormone, or GIP. And all these hormones have an effect on the Langerhans islet on the alpha and the beta cell over there. And they modulate the secretion of glucagon and insulin, especially in the postprandial situation and thereby modulate the postprandial glucose levels in our body.
And if you look now into the GLP-1 and the GIP in a little bit more detail, you see in the postprandial situation GIP from the K-cells is responsible for the majority of the insulin secretion in that postprandial situation, around 44%. And if you go to the lower end of this slide, there you see the effect of GLP-1 in healthy volunteers, and you recognize that it's much less, it's around 22%. Glucose by its own without these two incretins does only account for around 1/3 of the insulin secretion. So that's the situation we have in our healthy people.
So these are the effects of GLP-1 and GIP on the pancreas, but there are a lot of other effects from GLP-1 which we have learned a lot from during the last years. We have central effects reducing the food intake, it has some effects which are adverse effects, nausea. And it has effects on body weight and on stomach we know that it reduces gastric emptying.
Other effects of GIP beyond the Langerhans islet, beyond alpha and beta cells, you see over here it has also central effects also reducing appetite, but through other neural pathways over here. What is very interesting is that GIP has important effects on the adipose tissue. And this is shown over here on the left side, you can see it increases blood flow in the adipose tissue in case of hyperglycemia and hyperinsulinemia, which is not the case in the case of hyperinsulinemia alone.
Then on the right side, you see this is a lipoproteinlipase activity, this is responsible for the uptake of free fatty acids into adipocytes. And you can clearly see the GIP increases this uptake of the free fatty acids into the adipocytes, which is not the case not at all if you add GLP-1 as you can see over here. It improves insulin sensitivity in the adipose tissue as you can see here. And it reduces the cytokine and adipokine release from the visceral adipose tissue, as you can see over here.
And then you have, of course, the systemic effects reduce in hyperglycemia with GLP-1 receptor agonists, and on the other side with GIP you also reduce the hyperglycemia and the postprandial triggers.
So let me conclude, GIP together with GLP-1 are responsible for the so-called incretin effect, which enhances the secretion of insulin after a meal in a glucose dependent body. GIP may help to maintain blood glucose levels in two ways. It enhances glucose-dependent insulin secretion from the beta cells on one hand, but it also improves insulin sensitivity as suggested by preclinical data, but also from lab studies now. And under experimental conditions in healthy humans, GIP enhances blood flow through the adipose tissue, it increases triglyceride clearance and glucose uptake in the adipose tissue after the ingestion of nutrients in the postprandial situation. So thank you very much.