Why Diabetics Over Produce Sugar in the Liver

Type 2 diabetics often suffer from an over-production of sugar within the liver, a response to falling blood glucose levels. This potentially dangerous mechanism was poorly understood until recently, when researchers uncovered the role that a certain “master regulator” plays in sugar production within the liver.

While an inability to regulate blood glucose levels, due to resistance to insulin produced by pancreatic beta cells, is the primary mechanism that leads to and enhances type 2 diabetes, the liver plays a large role as well. Beta-cells, in a healthy body, produce insulin, which helps regulate blood glucose levels, but the liver itself directly responds to low blood glucose levels by producing more sugar. In type 2 diabetics, who suffer from insulin resistance (and therefore dysfunctional regulation of blood glucose with insulin), the liver often has a tendency to produce sugar when not really needed, which can cause potential harm. In other words, the liver continues to produce sugar past what it should, because insulin is not regulating the sugar already being produced, in type 2 diabetics.

To illustrate the role that the liver plays in type 2 diabetics, researcher Dr. Jenny Gunton explains that over-production of sugar within the liver is why many diabetics wake up with higher blood glucose levels than they had when going to sleep: “…It upsets people when their blood sugar behaves as if they’re getting up in the night and having a really big snack. I have to tell them it’s just one of those unfair things about having diabetes.”

Researchers looked at ARNT, a so-called “master regulator,” which is known to play a large role in insulin production and blood glucose control. Past research by the same research team demonstrated that type 2 diabetics have 90% less ARNT in insulin producing pancreatic beta cells, than non-diabetics.

The current study focused on ARNT’s role in the liver, through analysis of an animal model. Researcher Dr. Jenny Gunton says of this research, “working with mice, we found that glucose levels were elevated and there was glucose production from a ‘precursor’, a source not normally metabolised.” Dr. Gunter expresses the general conclusion that can be drawn from this, saying, “we’ve shown that there’s likely to be decreased ARNT in the liver of people with Type 2 diabetes compared to people without Type 2 diabetes.”

Further, it was observed within the mice, that insulin resistance directly contributed to lower levels of ARNT. “Treating” liver cells with insulin therefore had the effect of slightly increasing ARNT levels, suggesting a potential treatment for this sugar over-production mechanism within the liver. Other potential treatments, which will focus on increasing ARNT levels, should be the objective of some future research.

Source: Defeat Diabetes Foundation: Gunton, Jenny. Heather, Alison. Cell Metabolism news release. May 2009.