Proven Link Between Obesity And Diabetes

[Lloyd]

Proven Link Between Obesity And Diabetes

A Monash University study has proven a critical link between obesity and the onset of Type 2 diabetes, a discovery which could lead to the design of a drug to prevent the disease.

The findings were published today in Cell Metabolism.

The team, led by Associate Professor Matthew Watt, discovered that fat cells release a novel protein called PEDF (pigment epithelium-derived factor), which triggers a chain of events and interactions that lead to development of Type 2 diabetes.

"When PEDF is released into the bloodstream, it causes the muscle and liver to become desensitised to insulin. The pancreas then produces more insulin to counteract these negative effects, " Associate Professor Watt said.

This insulin release causes the pancreas to become overworked, eventually slowing or stopping insulin release from the pancreas, leading to Type 2 diabetes."

"It appears that the more fat tissue a person has the less sensitive they become to insulin. Therefore a greater amount of insulin is required to maintain the body's regulation of blood-glucose," Associate Professor Watt said.

"Our research was able to show that increasing PEDF not only causes Type 2 diabetes like complications but that blocking PEDF reverses these effects. The body again returned to being insulin-sensitive and therefore did not need excess insulin to remain regulated."

Associate Professor Watt said identifying the link is a significant breakthrough in explaining the reasons why obesity triggers the onset of Type 2 Diabetes.

"Until now scientists knew there was a very clear pattern and had strong suspicions that a link existed between the two conditions, but our understanding of the chain of events that are caused by the release of PEDF shows a causal link," Associate Professor Watt said.

"Type 2 diabetes patients will benefit knowing the two conditions are linked. We already know that weight-loss generally improves the management of blood glucose levels in diabetes patients. Researchers can now move forward knowing this link exists and we can begin to design new drugs to improve the treatment of Type 2 diabetes," Associate Professor Watt said.

Source:
Samantha Blair
Monash University

[foxl]

So we could theoretically counter the effects of PEDF or suppress it, and do away with insulin resistance?

Where is Monash Univ.? Ah, answered myself -- Melbourne.

[Subby]

I don't know definitively, but Monash is among the better established and well regarded unis in Melbourne/Australia.

[foxl]

It would be interesting to look at variation in secretion among members of a population ... perhaps covariance with IR or weight.

And it is of interest because it does a few other things in the body, as well ... pigment epithelium-derived factor - Google Search

[xMenace]

The pancreas then produces more insulin to counteract these negative effects, [/B]" Associate Professor Watt said.

This insulin release causes the pancreas to become overworked, eventually slowing or stopping insulin release from the pancreas, leading to Type 2 diabetes."

IMO you can replace these words with

"When you eat a high carbohydrate diet, the pancreas then produces more insulin to cover these carbohydrates. This insulin release causes the pancreas to become overworked, eventually slowing or stopping insulin release from the pancreas, leading to Type 2 diabetes."

This first practice also leads to obesity in many which exacerbates the whole mess.

[Nita]

I can remember when I first developed diabetes a doctor acquaintance (not my own doctor that was treating me) told me, "You have diabetes because you are fat and you are fat because you have diabetes."

I never could quite understand that then but boy it is such a struggle.....more weight added after insulin.

Nita

[Cain]

Sounds about right. My just found grandfather told my mother that he is a diabetic, but he lost the weight he put on and now is completely off meds. Don't know if that means he is "cured", but sure seems like a link there.

[slipperyelm]

IMO you can replace these words with

"When you eat a high carbohydrate diet, the pancreas then produces more insulin to cover these carbohydrates. This insulin release causes the pancreas to become overworked, eventually slowing or stopping insulin release from the pancreas, leading to Type 2 diabetes."

This first practice also leads to obesity in many which exacerbates the whole mess.

I don't think it is slowed or stopped insulin release which leads to diabetes. I once read that Type 2s might have nearly 20 times as much endogenous insulin in their bloodstream as does a non-diabetic person. Diabetes exists well before there is an insulin decrease.

[volleyball]

Cures come along all the time. Then they fade away. Proof comes when people are cured.

[REDLAN]

Abstract wrote
Obesity is a major risk factor for insulin resistance; however, the factors linking these disorders are not well defined. Herein, we show that the noninhibitory serine protease inhibitor, pigment epithelium-derived factor (PEDF), plays a causal role in insulin resistance. Adipocyte PEDF expression and serum levels are elevated in several rodent models of obesity and reduced upon weight loss and insulin sensitization. Lean mice injected with recombinant PEDF exhibited reduced insulin sensitivity during hyperinsulinemic-euglycemic clamps. Acute PEDF administration activated the proinflammatory serine/threonine kinases c-Jun terminal kinase and extracellular regulated kinase in both muscle and liver, which corresponded with reduced insulin signal transduction. Prolonged PEDF administration stimulated adipose tissue lipolysis, resulted in ectopic lipid deposition, and reduced insulin sensitivity, while neutralizing PEDF in obese mice enhanced insulin sensitivity. Overall, these results identify a causal role for PEDF in obesity-induced insulin resistance.

So to summarise the study consisted of injecting mice with PEDF, and they discovered that insulin resistance increased. As an investigation this is a good way of demonstrating that PEDF is a causal factor in the changes in IR observed in mice.

However the conclusions about type 2 and obesity can not be substantiated as a causal mechanism. Why?

because most people who are obese do not develop type 2 - what we have is a plausible mechanism as to one of the factors that cause the rise in insulin resistance with BMI (still needs to be demonstrated in humans)

one other factor to bear in mind PEDF is also produced by other tissues in the body, and it has multiple functions - including tumour growth suppression, anti-inflammatory properties, and protective functions in neurones. Developing anti-PEDF drugs could come with some nasty side-effects

I really don't like science by press release