The Pancreas is the First Organ to Fail in Type 2 Diabetes
There is no Such Thing as a Touch of Diabetes
The pancreas is the first organ to fail in type 2 diabetes. The same biology that causes pancreatic failure speeds up failure in other organs later when high glucose further increases oxidant production. This organ is very vulnerable to oxidant damage and it has very limited antioxidant production. Pancreatic failure is advanced early in the diabetes process. There is no such thing as early diabetes or a touch of diabetes. By the time an individual is first diagnosed with diabetes, significant insulin production has been lost.
Just as with organ damage in other chronic diseases. mTOR (mechanistic target of rapamycin) plays a critical role in this change. mTOR activity is essential to support normal pancreas growth in children. Later in life chronic, excessive intake of fast food and soul food persistently activates mTOR, which kills or sickens the cells in the pancreas that make insulin. In overweight individuals, mTOR is persistently and strongly switched on. That also increases resistance to insulin effects. In other words, it takes more insulin to lower the blood sugar to the same extent. In normal circumstances, when eating moderate amounts of food intermittently in lean individuals, intermittent mTOR activity acts to support the cells that make insulin. Excessive, persistent mTOR activity kills them or makes them sick so they cannot produce insulin. It reduces insulin output. In youngsters, sustained mTOR activation increases insulin production. In older people, it kills insulin producing cells and reduces insulin production leading to diabetes. This is consistent with a pattern in other organs. Regeneration is possible in younger individuals, but in older patients the same signaling leads to functional cell loss, scarring, and ultimately organ failure.
The beta cells in the pancreas die or become sick in prediabetes and type 2 diabetes. These are the functional cells in that organ that make insulin. Once the sugar level increases above the normal range, that means insulin producing capacity is reduced and beta cells are sick or dying. In circumstances of poor sugar control and high triglycerides, insulin production progressively declines. High fat and sugar levels in the blood add to the stress that is destroying the pancreas. As with other organ failure, that is only half of the story. As the functional cells are lost the organ is injured, and functional cells are replaced by scar tissue. Metformin has many effects, but most of these flow from its main action. Metformin directly inhibits the master metabolic genetic switch mTOR and activates AMPK (AMP kinase). Scar tissue formation is a major part of pancreatic cancer biology. In that setting metformin inhibits scar tissue formation and slows pancreatic cancer progression. Pancreatic cancer is the fourth leading cause of cancer death. Survival rates are extremely poor. Some studies show a substantial reduction in the number of patients with diabetes who develop pancreatic cancer if they are on metformin.
This information is extremely valuable to patients who struggle with type 2 diabetes. It explains why certain treatments prolong lives and reduce complications more than other treatments. It explains why some treatments don’t simply lower the sugar, they protect vital organs like the eye, heart, and kidney. Oxidants activate growth factors which activate mTOR and inactivate AMPK. Lisinopril, losartan, spironolactone, and eplerenone are all antioxidants that indirectly inactivate mTOR and activate AMPK. Metformin directly inhibits mTOR and activates AMPK. Empagliflozin activates AMPK and inhibits mTOR. Reducing calories, intermittent fasting, and exercise do the same thing. Our treatments for type 2 diabetes are much better now. We can all reduce the toll of premature death and disability from this terrible disease. We can extend the lives of patients with type 2 diabetes an average of 8 years.
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