Why High Blood Sugar is Bad News for Calcium ATPase

Sugar cubes, a donut, and the word Diabetes draw attention to its relationship with Calcium ATPase
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We learned about the link between calcium, high blood sugar, and Calcium ATPase in our previous blog post. If someone’s body cannot process blood sugar correctly, because of low insulin, or inability to use insulin, they have diabetes. 

Diabetes is a complicated health condition linked to Calcium ATPase. This key health indicator protects cells from calcium overload and ensures there’s enough calcium in the endoplasmic reticulum for insulin production. If not, insulin production decreases, triggering stress hormones, and the death of insulin-producing beta cells. 

Essentially, healthy Calcium ATPase levels contribute to regular blood sugar. 

The link between high blood sugar and Calcium ATPase

Knowing what we do about Calcium ATPase it would seem logical if high blood sugar or hyperglycemia triggered increased levels. However, this is not the case, and hyperglycemia caused by diabetes inhibits Calcium ATPase in many of the body’s organs. 

Although ironic, it’s important to understand because this reduction in Calcium ATPase contributes to many diseases associated with diabetes, including heart disease, hypertension (high blood pressure), sensory neuropathy (nerve damage causing weakness, numbness, and pain), and cataracts. 

There are two reasons hyperglycemia harms Calcium ATPase:

  1. The formation of advanced glycation end products that disable Calcium ATPase 
  2. Oxidation by free radical damage to Calcium ATPase  

 

Yes, it sounds complicated! Let’s explore each of those causes in more detail. 

Advanced Glycation End Products (AGEs) 

The definition of AGEs tells us they are proteins or lipids that become glycated in the presence of sugars. In simple terms, glycation is when a sugar molecule attaches.

In diabetes, when blood sugar levels are higher than average, it’s more likely that AGEs form. 

AGEs are biomarkers implicated in the aging process and development or worsening of degenerative diseases, like diabetes, atherosclerosis (buildup of fatty plaques in the arteries), kidney disease, and Alzheimer’s.

Recall that Calcium ATPase is a protein. In diabetes, the condition increases AGE formation on Calcium ATPase, which upsets how well it can transport calcium. AGEs are not unlike parasites. They attach themselves to the host, in this case, proteins like Calcium ATPase or lipids. They stop the host molecule from working correctly and eventually cause its death.

Oxidation by free radical damage to Calcium ATPase 

The other way hyperglycemia reduces Calcium ATPase is through free radicals. 

Hyperglycemia generates reactive oxygen species (ROS). ROS are molecules with an unpaired electron in one of its orbits, called a free radical or oxygen radical. Normal molecules have a balanced number of electrons or negatively charged particles that surround the core. When an electron doesn’t have a partner, this destabilizes the whole molecule, making it reactive.

The ROS wants to rid itself of the unpaired electron, so it donates it to another molecule. When a molecule does this, we call it an oxidant, and it oxidizes the other molecule. A buildup of ROS in cells may cause damage to DNA, RNA, and proteins and can cause cell death. Calcium ATPase is one protein that ROS can damage when the body is in a state of high blood sugar. 

Diabetes-related diseases and Calcium ATPase

The combination of diabetes, related high blood sugar, and reduced Calcium ATPase causes damage throughout the body and many diseases, including:

  • Heart disease
  • High blood pressure
  • Sensory neuropathy
  • Vision problems 

Heart disease

Heart disease is the leading cause of death in people with diabetes. Diabetic cardiomyopathy, to use its specific name, is heart failure, which is progressive and incurable. 

Animal research shows reduced Calcium ATPase levels in the hearts of diabetic rats. Calcium ATPase levels can be 50% lower in this group, which relates to reduced heart muscle contraction and relaxation. 

High blood pressure

Two-thirds of people with diabetes have high blood pressure and need to use medication. 

Researchers considered the link between reduced Calcium ATPase and high blood pressure in people with diabetes. They found reduced Calcium ATPase levels in those with insulin-dependent and non-insulin-dependent diabetes compared to control subjects. 

Not only this, but there was a significant correlation between systolic blood pressure, which measures the heart’s beating force, and Calcium ATPase activity in insulin-dependent and non-insulin-dependent patients.

Sensory neuropathy

Sensory neuropathy is the medical name for nerve damage. Approximately 50% of people with diabetes have the condition. The most common symptoms of sensory neuropathy are tingling, numbness, and pain. People may also have a reduced ability to sense pain or extreme temperatures, which can lead to injuries.

Nerve cells rely on intracellular calcium changes to transmit nerve signals, meaning Calcium ATPase plays a central role in nerve function.

When researchers looked at sensory neurons in rats, they found a two-fold reduction of Calcium ATPase activity in the diabetic group.  

Vision problems

Cataracts affect 66% of those with diabetes. People with diabetes have a greater risk of complications, including blindness during cataract surgery. 

Studies show increased intracellular calcium levels and low Calcium ATPase affect cataract formation in diabetic animals.

Calcium ATPase is at the root of diabetes and related health conditions

Calcium ATPase is linked to diabetes because of its essential role in pancreas function, where insulin is produced and released. 

In addition, high blood sugar reduces Calcium ATPase levels resulting in disease states associated with diabetes, like heart disease, high blood pressure, and sensory neuropathy.

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Calcium Atpase (CA2+ATPASE Molecule) - Illustration