UCSD Jacobs School of Engineering

Fast-Food Breakfast Combo May Feature Digestive Enzymes on the Prowl and Diabetes

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San Diego, Calif., May 28, 2019 -- Thinking about getting in the car to pick up breakfast at a fast-food joint? Hit the brakes and chew on this: High-calorie, high-carb meals – like the one you’re about to chow down – may be driving your gut to leak your digestive enzymes and accelerating insulin resistance.

We know you’ve heard it before, the Western diet is tied to an increase in diabetes. In fact, 1.5 million Americans are newly diagnosed each year.

In a paper recently published online in the Journal of the American College of Nutrition, physicians and bioengineers at the University of California San Diego used a new set of fluorescent peptides to illuminate a molecular digestive enzyme mechanism that occurs after consumption of a typical fast-food chain American-style breakfast, one that may be contributing to the prevalence of type 2 diabetes.

This method to detect the mechanism was developed by Michael Heller of the Oregon Health and Science University and Geert Schmid-Schonbein, a professor in the Department of Bioengineering at UC San Diego. Heller’s Ph.D. student Augusta E. Modestino, now at OHSU, is the study’s first author.  Heller and Schmid-Schonbein worked with Paul J. Mills, professor and chief of Family Medicine and Public Health at UC San Diego Health, who secured clinical samples from patients. 

The study included sampling blood from 30 volunteers before and after feeding them a breakfast comprised of one McDonald’s Egg McMuffin, two hash browns, a glass of orange juice and one McCafé hot chocolate. Ten participants were healthy, 10 had prediabetes and 10 had been previously diagnosed with type 2 diabetes.

The study showed that after every high fat meal, people leak digestive enzymes into their blood circulation, said Schmid-Schonbein. This in turn causes the enzymes to clip cell receptors for insulin, leading to insulin resistance and an increased risk of type 2 diabetes.

“I look at this as direct supporting evidence that there is autodigestion, not just digestion,” Schmid-Schonbein said.

Schmid-Schonbein is a leading expert on the phenomenon of autodigestion, in which digestive enzymes are released out of the gastro-intestinal tract and start digesting cells and tissue, leading to disease.

Last year, he lead an international team of researchers to uncover a destructive mechanism at the molecular level that causes a well-known phenomenon associated with obesity, called leptin resistance.

They found that mice fed a high-fat diet produce an enzyme named MMP-2 that clips receptors for the hormone leptin from the surface of neuronal cells in the hypothalamus. This blocks leptin from binding to its receptors. This in turn keeps the neurons from signaling that your stomach is full and you can stop eating. 

This was the first time that a molecular mechanism for destruction of membrane receptors has been observed and described following a high fat meal (In Science Translational Medicine).

In 2013, Schmid-Schonbein and colleagues discovered that acute insulin resistance in shock patients is caused by the leakage of powerful digestive enzymes from the small intestine that eat away and destroy the insulin receptor in cells. Reporting online in the journal Shock, the team has also found a way to stop these enzymes’ destructive path by blocking them in the intestine, where they are normally used to digest food.

In the Q&A below, senior author Mills, director of the Center of Excellence for Research and Training in Integrative Health at UC San Diego School of Medicine, talks about the study’s main findings.

What were you looking for in this study?

A high-calorie diet is a major risk factor for the development of type 2 diabetes and is also associated with an increased permeability of the intestinal mucosa or “leaky gut” – a condition that occurs when the barrier function of the lumen (the lining of the intestinal wall) is compromised and allows bacteria, toxins, or in this case digestive enzymes, to seep out of the intestines. We wanted to see if there was a nutritional link.

And the answer is yes. In this study we detail evidence for the hypothesis that the digestive system, and in particular pancreatic proteases (enzymes that break down proteins and peptides – short chains of amino acids – to facilitate digestion) are significantly increased in the peripheral circulation following a high-calorie meal and may be associated with the development of insulin resistance and type 2 diabetes.

What did you see in the blood?

What we found was that before the study participants ate a McDonald’s breakfast, the healthy control group did not have much evidence of protease activity in their blood. People with prediabetes already had a degree of the enzyme activity in their blood and the diabetics had the highest levels of the enzyme activity in their blood.

After eating the high-calorie, high-carbohydrate meal, everyone had increased activity of the enzymes in their blood, but the control group began to return to their pre-meal levels after 30 to 60 minutes. It took longer for prediabetics and diabetics to return to their pre-meal activity levels, and they also had significantly increased activity levels in response to the meal as compared to the healthy group.

 

What’s the connection to type 2 diabetes?

When pancreatic enzymes leak into the blood, they don’t turn off their function. They continue to digest proteins and we found that this function included a rapid digestion of insulin receptors, which would make it tougher for people to regulate their glucose. People with diabetes had more of this enzyme activity in their peripheral circulation, independent of these meals, but also a further significant increase and highest response to the meal.

They may have developed their chronic glucose-regulation problem as a result of continued exposure to such high-calorie meals and consequent digestion of their insulin receptors. People with prediabetes may be able to turn this condition around. We have seen that a healthier diet can reverse prediabetes and the molecular activity we saw occurring after eating the high-calories meals may be pointing to the mechanism.

What can be done?

In addition to simply avoiding such meals, there are compounds we can take that can inhibit protease activity in the peripheral circulation. Our research team is looking to conduct a randomized clinical trial to see if we can help inhibit pancreatic enzyme activity in the blood and restore insulin receptor integrity, whether through inhibitors or a moderate diet.

The overarching finding is that high-calorie meals that so many Americans eat, especially through different fast food venues, damages intestine integrity so that pancreatic enzymes leak out into peripheral circulation. We should all look at our meals and eat well.

This is something that people can act on today. Things we can do behaviorally to support our health.

 

– Yadira Galindo

 

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