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Lab+Life Scientist Aug/Sep 2022

Page 30

Diabetes drug

to correct metabolic abnormalities Type 2 diabetes is a major public health problem that affects millions of people worldwide, so developing new drugs to help better treat its underlying causes is something of a priority. An international team of scientists has now developed a peptide known as PATAS, part of a new class of antidiabetic drugs, which can correct the metabolic abnormalities leading to type 2 diabetes and its associated comorbidities — including insulin resistance.

T

© iStockphoto.com/VioletaStoimenova

pharma

The researchers then went on to focus more closely on ALMS1 and how it interacts with other proteins within the adipocytes. In particular, they have shown that in the absence of insulin, ALMS1 binds to another protein called PKC alpha. The activation of insulin in the adipocytes induces the separation of ALMS1 and PKC alpha, resulting in glucose entry into cells. In people with diabetes, who are insulin-resistant, this link between the two proteins is maintained.

The role of adipocytes

Drawing on this knowledge, the scientists

In previous research, published in 2020, the research

developed the peptide PATAS, which works by

team had identified a new therapeutic target for

breaking the interaction between ALMS1 and PKC

type 2 diabetes when investigating an ultra-rare

alpha — thus restoring insulin signalling in the

he prevalence of type 2 diabetes, which is

monogenic disease known as Alström syndrome.

adipocytes. Their latest study, conducted on animal

characterised by high levels of glucose in the blood,

They showed that adipose tissue abnormalities

models and published in the journal Diabetes,

has been increasing for decades due to population

caused by a dysfunctional protein called ALMS1 led

confirms that PATAS restores glucose uptake in

aging, inactivity and poor diet. Available drugs treat

to extremely severe insulin resistance associated with

the adipocytes, resulting in the treatment of insulin

the consequences of type 2 diabetes by focusing mainly

early-onset type 2 diabetes in people with Alström

resistance with beneficial effects on the whole body.

on lowering blood glucose, but they do not target

syndrome. In animal models, restoring the function

“Thanks to PATAS, the adipocytes that could no

the underlying biological mechanism that causes

of this protein within the adipocytes re-established

longer access glucose were once again able to absorb

the disease. Furthermore, despite the need for new

blood glucose balance.

it and then metabolise it in order to synthesise and secrete lipids which are beneficial to the entire body,”

disruptive therapeutic innovations to reach market

Marion said. “These positive effects are visible in our

in over a decade. This is the objective of the research led by Vincent Marion, from the French National Institute of Health and Medical Research (Inserm), and his team at the University of Strasbourg. In collaboration with the

Image courtesy Vincent Marion.

and more effective treatments, there have been no

animal models, with a marked improvement in insulin resistance. Other parameters and comorbidities are also improved, including better blood glucose control and decreased liver fibrosis and steatosis.” The successful development of a new class of

University of Birmingham and Monash University,

antidiabetic drugs could have significant implications

the scientists developed a product called PATAS

for public health, not only to treat type 2 diabetes but

in a new class of diabetes drugs called ‘Adipeutics’. PATAS works by specifically targeting the adipocytes (fat cells), restoring glucose entry and thus correcting and re-establishing the metabolic physiology of the adipose tissue.

30 | LAB+LIFE SCIENTIST - Aug/Sep 2022

also many other cardio-metabolic disorders in which Mouse visceral adipose tissue fluorescently labelled; nuclei coloured blue.

dysfunctional adipocytes and insulin resistance are problematic. And with promising results in animals, the researchers plan on organising a clinical trial as soon as possible, in order to test PATAS in humans.

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