Newly diagnosed type 2 diabetics tend to have one thing in common: obesity. Exactly how diet and obesity trigger diabetes has long been the subject of intense scientific research. A new study published online August 14 in Nature Medicine reveals a pathway that links high-fat diets to a sequence of molecular events responsible for the onset and severity of diabetes.
In studies spanning mice and humans, a research team at the Center for Nanomedicine, a collaboration between Sanford-Burnham and the University of California, Santa Barbara, discovered a pathway to disease that is activated in pancreatic beta cells, and then leads to metabolic defects in other organs and tissues, including the liver, muscle and adipose (fat). Together, this adds up to diabetes.
“We were initially surprised to learn how much the pancreatic beta cell contributes to the onset and severity of diabetes,” says Dr. Jamey Marth, director of the Center for Nanomedicine and senior author of the study. “The observation that beta cell malfunction significantly contributes to multiple disease signs, including insulin resistance, was unexpected. We noted, however, that studies from other laboratories published over the past few decades had alluded to this possibility.”
In healthy people, pancreatic beta cells monitor the bloodstream for glucose using glucose transporters anchored in their cellular membranes. When blood glucose is high, such as after a meal, beta cells take in this additional glucose and respond by secreting insulin in a timed and measured response. In turn, insulin stimulates other cells in the body to take up glucose, a nutrient they need to produce energy.
In this newly discovered pathway, high levels of fat were found to interfere with two key transcription factors—proteins that switch genes on and off. These transcription factors, FOXA2 and HNF1A, are normally required for the production of an enzyme called GnT-4a glycosyltransferase that modifies proteins with a particular glycan (polysaccharide or sugar) structure. Proper retention of glucose transporters in the cell membrane depends on this modification, but when FOXA2 and HNF1A aren’t working properly, GnT-4a’s function is greatly diminished. So when the researchers fed otherwise normal mice a high-fat diet, they found that the animals’ beta cells could not sense and respond to blood glucose. Preservation of GnT-4a function was able to block the onset of diabetes, even in obese animals. Diminished glucose sensing by beta cells was shown to be an important determinant of disease onset and severity.
Pancreatic beta cells from mice fed a standard diet (left) or a high-fat diet (right). (glucose transporters=green, insulin=red, DNA=blue) (Image courtesy of the Marth lab)
“Now that we know more fully how states of over-nutrition can lead to type 2 diabetes, we can see more clearly how to intervene,” Dr. Marth says. He and his colleagues are now considering various methods to augment beta cell GnT-4a enzyme activity in humans, as a means to prevent and possibly cure type 2 diabetes.
“The identification of the molecular players in this pathway to diabetes suggests new therapeutic targets and approaches towards developing an effective preventative or perhaps curative treatment,” Dr. Marth continues. “This may be accomplished by beta cell gene therapy or by drugs that interfere with this pathway in order to maintain normal beta cell function.”
In the United States, more than 24 million children and adults—nearly eight percent of the population—have diabetes. In adults, type 2 diabetes accounts for about 90 to 95 percent of all diagnosed cases of diabetes.
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Original paper:
Ohtsubo, K., Chen, M., Olefsky, J., & Marth, J. (2011). Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport Nature Medicine DOI: 10.1038/nm.2414
hi, i am rama gobinda iam from india my wife is diabetes patient she regularly takes insulin 2 times a day now she is pregnant her sugar label shuld not down . her fasting label 190 and p.p is 240 what to do pls advice me. in pregnant stage which medic-en is better to her
what is the best herbal medicine in diabetes?
my name is imtiaz ahmed in the age of 52 i come to know that i m diabetic my all feeling are quite normal please advise me accordingly thanks
Which kind of peoples are affected by diabetes.
I would also like to know at what age
My name is charles wyte, why diabes being cure by some people after taking there drugs for a period of time, and in other people it does’nt work that way why? Please tell me!
I am diabities type 2. what permanent treatment for me.
so after knowig how diabetes is brought about, what are some of the measures on can take to reduce diabetes and probably what foods should a diabetic feed on so as to reduce the glucose development in the blood sys. the medicine that can regulate the beta cell function.
i wish to know more about diabetic cause and symptoms
Having diabetes type -1 can I be able to allow my wife to adopt child ? Is there any possibility to have by born diabetes baby? Please suggest me in my mail.
my name is arjun kumar I am daibities passent what is the permanent treatment of daibities. pl. informed me very soon.
thanks
arjun
i sympathize for what i saw , my name is jabar kareem i studied at o.o.university my dad is a very specialist to diabetes and stroke, i don’t no if you don’t mind in reaching my mail so i can tell you a lot of what causes diabetes so you can know how to cautioned your self
my age is 25 and i am diabetic my fasting level is always above 200 please give me some advice so that i can control my diabetis
Is there treatment for diabetes?
Can diabetes be treated using herbal medicine?
Hi Ssendijja – Please consult a qualified medical doctor about options for treating diabetes.
Best,
Heather
I AM SUFFRING HIGH SUGAR LEVEAL DAIBITIC PESENT, PLEASE HELP GOOD MADICINE
FOR THIS MY AGE 54 YEARS MAIL SUFFRING LAST FOUR YEARS
Good day
i’m a recently diagnosed Diabetes; i am 1,74 m, men living in Cameroon an African country. I need your assistance and help because all my family is subject to be a diabetes
tank for that
NB: I am french speaking
can you tell me more about if the environment or genetics is the main cause for type 2 diabetes..keep in mind that im only 15 years old
I am also a Type 2 Diabetic that is 46 years old .
I often get dizziness .What can i do?
hi, I am a diabetes, I take insulin for 3 years, I feel toe numb 3 month ago, my friends sent me the pro duct named Gluconature, herbal supplement for diabete, Now though my blood sugar level does not reduce, but I feel better, my toe feel light numb, and I have a good appetite, do you I continue to take the product? this its website: http://www.gluconature.com
Hi there,
I’m a recently diagnosed Diabetes 2 person. I’m 62,female, live in Australia. Trying to get this under my control and know I’m to blame to a large degree but also furious at the powers that be. Why? Because they’ll get rid of smokes but not our worst KILLER which is SUGAR.It ‘s in everything we buy!!! Why can’t the medical fraternity turn their powers on the governments of the world and make them do something , like taking it out of all processed food. That’s my gripe with the Aussie govenment at the moment. We need to save lives and money to invest in those illness we can’t yet do much for.
I respect what you are doing and wish you the best and I will now do my bit as far as my diabetes goes.
Kind Regards
Dianne Roger
Down Under