The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 7 • November 2015


AUTOPHAGY AGAINST TYPE II DIABETES

Pancreatic Beta Cells Protected By Autophagy Against Amyloidogenic Degradation That Induces the Onset of Type II Diabetes

Aggregates of Amyloid Involved in Type II Diabetes Very Similar to the Aggregates of Neurotoxic Amyloid in Alzheimer’s Disease

TREHALOSE, An Inducer of Autophagy, May Be a Possible Protectant Against Amyloid Aggregation

VITAMIN D3 Induces Autophagy, Protects Against Inflammation and Infection

Following a trail of damaging mechanisms that cause type II diabetes, we find that an important source of protection is the process of autophagy.1 A new paper1 reports on how the loss of autophagy along with beta cell expression of IAPP (amyloid islet polypeptide, also called amylin), a 37 amino acid protein coexpressed and released by pancreatic beta cells along with insulin, results in the death (apoptosis) of beta cells. IAPP forms amyloid deposits in beta cells remarkably similar to the amyloid deposits that form in the brain during Alzheimer’s disease; these deposits are composed of aggregated, misfolded proteins that are normally cleared by the process of autophagy. In the absence of adequate autophagy, the toxic effects of IAPP deposits induces endoplasmic reticulum stress that kills beta cells and can, in that way, lead to type II diabetes.

In the paper (Rivera, 2014) the researchers report on their experiments with rodent beta cell islets, showing that when autophagy was stimulated by the autophagy-inducing drug rapamycin that (at the dose used) beta cell IAPP content was reduced by 54% ±5.5% versus untreated (no rapamycin) cells. More interestingly, since the rodent form of IAPP does not form amyloidogenic aggregated, misfolded cytotoxic deposits, the researchers duplicated their experiments using HUMAN islets and found that rapamycin decreased IAPP content by 31% ±12.4% as compared to untreated human islets.

The researchers cite a paper (one which we already had) (Zang, 2007) that listed a number of FDA-approved drugs that, like rapamycin, had also been found to have autophagy-enhancing effects. What is particularly interesting among these identified autophagy-enhancing drugs is the safe and relatively inexpensive over-the-counter drug loperamide, which is used to treat diarrhea. (Not unsurprisingly, one possible side effect of using too much is constipation. Side effects of the drug are generally mild. Though loperamide is a mu opioid agonist, it does not pass the blood-brain barrier except in those rare individuals with “leaky” blood-brain barriers.)

The researchers conclude that their paper presents “the first line of evidence” that establishes a protective effect of autophagy against human IAPP-induced toxicity in human beta cells and protects the cells from being killed, part of the process resulting in type II diabetes. They propose “the players of the autophagy pathway as key therapeutic targets for treatment and prevention of T2D [type 2 diabetes].” (Rivera, 2014).

Enhancing Autophagy With TREHALOSE or Loperamide

If you have type II diabetes and would like to try loperamide to induce autophagy to possibly improve your diabetes, we suggest you follow the label instructions. The limited amount of loperamide as given on the label is particularly aimed at avoiding constipation, but if you are under the supervision of a physician, you might ask him or her about taking up to twice that amount and simply reducing your dose if you encounter constipation.

Note that TREHALOSE, the natural osmolyte that acts as a chaperone to help proteins fold properly (found in our protein folding formulation), is also an inducer of autophagy. In a different paper on autophagy, IAPP, and the development of type II diabetes, TREHALOSE was used to induce autophagy to promote clearance of the amyloidogenic IAPP in mice fed a high fat diet (Kim, 2014).

VITAMIN D3 Is Another Natural Inducer of Autophagy

Recent research (Wu, 2011) reports that VITAMIN D3 induces autophagy in and provides protection during inflammation and infection. “Vitamin D deficiency is a critical factor in the pathology of at least 17 varieties of cancer, as well as autoimmune diseases, diabetes, osteoarthritis, periodontal disease, and more.” (Wu, 2011) “Autophagy … plays important roles in the degradation of damaged cytosolic components and misfolded proteins and in organelle turnover.” (Yuk, 2009).

References

  • Cheng et al. Coffee components inhibit amyloid formation of human islet amyloid polypeptide in vitro: possible links between coffee consumption and diabetes mellitus. J Agric Food Chem. 59:13147-55 (2011).
  • Huxley et al. Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus. Arch Intern Med. 169(22):2053-63 (2009).
  • Kim, Cheon, Jeong, Quan, et al. Amyloidogenic peptide oligomer accumulation in autophagy-deficient beta cells induces diabetes. J Clin Invest. 124(8):3311-24 (2014).
  • Rivera et al. Autophagy defends pancreatic beta cells from human islet amyloid polypeptide-induced toxicity. J Clin Invest. 124(8):3489-3500 (2014).
  • Wu and Sun. Vitamin D, vitamin D receptor, and macroautophagy in inflammation and infection. Discov Med. 11(59):325-35 (2011).
  • Yuk, Shin, Lee, et al. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. 6:231-43 (2009).
  • Zhang et al. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci U S A. I 104(48):19023-8 (2007).

Featured Product

  • Learn more about Vitamin D3 benefits and implementation strategies.

Ingredients in this Article

FREE Subscription

  • You're just getting started! We have published thousands of scientific health articles. Stay updated and maintain your health.

    It's free to your e-mail inbox and you can unsubscribe at any time.
    Loading Indicator