How Diabetics Reduce Ceramides

Diabetes can be classified into two groups based on its pathophysiology. The autoimmune destruction of B-cells causes Insulin-dependent diabetes. In contrast, Non-insulin-dependent diabetes the other is due to the progressive decline of pancreatic B-cell function in the context of insulin resistance. The primary disease threats of diabetes are often microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular (cardiovascular diseases) complications.

Lipids accumulation in adipocytes or non-adipose tissue (muscle, liver) causes chronic inflammation caused by adipocyte hypertrophy (a feature of dysfunctional adipose tissue). The sphingolipid ceramide is the one that combines an abundance of nutrients (saturated fatty acids) and small inflammatory proteins to the development of insulin resistance. The accumulation of sphingolipid ceramide in tissues of obese humans is in line with diabetes, hypertension, cardiac failure, or atherosclerosis. After adipocytes exceed their storage capacity in hypertrophied fatty tissue, neutral lipids accumulate in non-adipose tissues, inducing organ dysfunction. 

What are ceramides?

Ceramides are lipids (fats) present naturally in the outermost layers of skin. 50% of the skin is composed of Ceramides, so it's no surprise they play an essential role in determining how your skin looks and how your skin responds to environmental threats.

What do Ceramides do?

Ceramides help the skin hold up together by creating a protective layer that limits moisture loss and protects against damage that is visible from pollution and other environmental stressors. Ceramides also have a great impact on how the body handles nutrients. They impair the way the body responds to insulin and how it burns calories. In addition, Ceramides —even more than retinol, niacinamide, and peptides are some of the anti-aging "powerhouses" responsible for supporting skin's dynamic nature. Two particular ceramide precursors are phytosphingosine and sphingolipids; these two help the skin to make more ceramides.

Diabetes and Ceramides

The concentration of Ceramides lipids in blood plasma and tissues can increase the risk of developing insulin resistance, and this causes people to have a greater chance of developing type 2 diabetes. This occurs when a build-up of Ceramides prevents the normal function of body fat tissue. For some people, excess fatty acids become Ceramides. When this happens, the Ceramides increase, the adipose (body fat) tissue stops working appropriately, and fat spills out into the vasculature or heart and damages other peripheral tissues.

People with high ceramides

Just like cholesterol, ceramides are sticky, fatty molecules that help maintain cell membranes and perform other critical life-sustaining tasks. If it is too much, both substances can destroy the cardiovascular system, creating a lot of plaque in the arterial walls. 

But recently, ceramides were much harder to find because they are 1,000 times fewer than cholesterol. New clinical tests are available, but they can only detect a small part of the ceramides circulating in the bloodstream. Although previous research has found a strong connection between circulating ceramide blood levels and coronary heart disease, the possibility of that risk had rarely been measured. 

Ceramides in Metabolic Syndrome

The development of insulin resistance is a critical step in developing metabolic syndrome, obesity, and diabetes. It occurs when the insulin level is high and is required to stimulate insulin-induced sugar intake, particularly in myocytes and adipocytes. Myocytes are the contractile muscle cells that make up the heart muscle, and adipocytes, known as lipocytes and fat cells, are the cells that primarily compose adipose tissue. 

Ceramides decrease the activity of Protein kinase B (PKB), which is a downstream effector of insulin signaling and apoptosis and cell proliferation. Furthermore, fat ceramide levels are higher in patients with increased hepatic lipid accumulation than those with healthy livers. Reduced Ceramides in your body prevent lipotoxicity caused by ceramide accumulation, preserving insulin and glucagon secretion. 

Role of Ceramides in Diabetes Mellitus

Diabetes mellitus is a kind of metabolic disease that has multiple complications that causes severe diseases over the years. The condition leads to severe complications in a person's body, and it is being known to more people these days. More research about this disease is being carried out to educate people about what this disease can do to your body and how it can affect you. Ceramide is a prime sphingolipid signaling molecule in the origination of type 1 and type 2 diabetes and its complications. Researchers and studies about this disease used cultured cells, animal models, and human subjects to demonstrate that ceramide has an essential role in inducing B-cell apoptosis, insulin resistance, and reducing insulin gene expression. Ceramide induces B-cell apoptosis by multiple mechanisms, namely, activation of the extrinsic apoptotic pathway, increasing cytochrome c release, free radical generation, induction of endoplasmic reticulum stress, and inhibition of Akt. Ceramide also modulates many insulin signaling intermediates such as insulin receptor substrate, Akt, Glut-4, and it causes insulin resistance. Ceramide reduces the synthesis of insulin hormone by attenuation of insulin gene expression. A better understanding of this disease will let us know the contribution of ceramide to the pathogenesis of diabetes and further help identify potential therapeutic targets for managing diabetes mellitus and its complications.

What removes Ceramides from the body? 

This was a suggestion that scientists made after finding out that they can reverse pre-diabetes by silencing an enzyme responsible for the final step of ceramide production.

Silencing the enzyme, called dihydroceramide desaturase 1 (DES1), can lower ceramide levels in the body. DES1 controls the conversion of dihydroceramide into ceramide by converting a slight chemical shift of two hydrogen atoms. This simple alteration effectively inserts a "double bond into the backbone" of the lipid molecule. 

Previous research had already suggested that reducing ceramide levels could potentially reverse metabolic disease and diabetes. However, the methods that they used would result in severe side effects. Researchers developed two ways of silencing DES1: the first one is, they silenced DES1 in the whole body. In other selections, they switched off the enzyme in selective locations, such as in the liver or fat cells.