Many individuals with type 2 diabetes wonder how their blood sugar levels can rise once they have not eaten anything. The answer to this paradoxical phenomenon lies in what’s generally known as Insulin resistance.
Insulin resistance prevents cells from taking over glucose properly, but it surely also causes the liver to proceed producing it. Here, we’ll have a look at how this happens, and current research being done to treat the condition.
Available energy
Normally, our blood glucose levels are controlled by a balance between the intake of this sort of sugar from food and its removal by the tissues. This balance is especially depending on the hormone insulin.
After a meal, an increase in blood glucose causes the beta cells of the pancreas to release insulin. This hormone facilitates the absorption, use and storage of glucose by the body’s tissues, ensuring that energy is accessible when the body needs it.
However, even when we go several hours without eating, the body still has to take care of a minimum level of glucose within the blood. This is to forestall hypoglycemia (low blood sugar), and to be sure that energy is supplied to tissues – especially the brain, which is nearly exclusively depending on glucose.
During the primary few hours of fasting, the liver breaks down the stored glucose and produces it. Glycogenthe shape by which glucose is stored within the body. As fasting continues and glycogen is depleted, the liver begins to synthesize glucose from noncarbohydrate precursors, a process Gluconeogenesis.
This mechanism is significant, since it ensures that our organs – and above all of the brain – proceed to operate once we fast.
A broken lock
Type 2 diabetes completely disrupts the traditional regulation of blood glucose levels, because it causes insulin resistance in patients.
An easy method to explain that is to consider insulin as a key that unlocks the cell’s door in order that glucose can enter and be used for energy. In a healthy person, the important thing suits perfectly into the lock. The door opens, and glucose moves from the blood into the cells.
But in patients with insulin resistance, the lock is flawed. Even though the body produces hormones and the keys can be found, the door doesn’t open wide enough. The result’s that a few of this glucose cannot enter the cells. Instead, it accumulates within the blood, causing Chronic hyperglycemia (high blood sugar).
But that is not the one purpose of insulin. Another essential function is to inhibit the production of glucose within the liver – a process called hepatic gluconeogenesis.
In type 2 diabetes, insulin resistance prevents insulin from acting properly, causing the liver to proceed producing glucose when it shouldn’t be needed. The result’s that blood glucose levels remain elevated, even on an empty stomach.
It has been reported that hepatic gluconeogenesis levels can range from low to high in individuals with type 2 diabetes. 40% to 200% More than healthy individuals.
For this reason, reducing hepatic glucose production has turn out to be a promising approach to enhance the efficacy of currently available treatments for lowering blood sugar levels.
New therapeutic targets
One of the possible keys to controlling excessive production of glucose by the liver in type 2 diabetes is a stress molecule called GDF15. Mice lack this molecule. Shows increased hepatic gluconeogenesis.suggesting that regulating its levels may help prevent glucose production within the liver.
Previous studies Treatment with it has been shown in patients with type 2 diabetes. Metformin – an antidiabetic drug commonly prescribed to treat type 2 diabetes, which works primarily by inhibiting hepatic gluconeogenesis – also increases GDF15 levels.
This suggests that a part of the drug’s antidiabetic effect could also be explained by its ability to extend GDF15 levels and, in doing so, reduce hepatic glucose production. Our research group recently observed this. This effect is not seen in GDF15-deficient mice.
Moreover, in our latest research we have now observed this. Metformin fails to increase. Blood levels of this molecule in mice lacking the PPARβ/δ receptor. This is probably going because PPARβ/δ is significant for the maturation of GDF15 and, consequently, for its increase in blood levels.
Taken together, these findings progressively reveal key aspects in GDF15 regulation and performance, offering promising recent avenues for improving glucose control in patients with type 2 diabetes.