Physiologic effects of MAT^® treatment

    MAT^®  treatment, Metabolic Activation Therapy, is a therapy for patients with severe complications of diabetes.   The treatment involves delivering insulin intravenously in a pulsatile fashion using a special type of pump over a six to seven hour period. The pulses deliver a higher, more physiologic concentration of insulin to the liver and other tissues than are delivered by traditional sub-cutaneous injections. This higher level of insulin stimulates liver cells and cells elsewhere in the body to synthesize glucokinase and other insulin-dependent enzymes necessary for normal dietary glucose processing and metabolic homeostasis.

Liver

In "normal" individuals, those without diabetes, insulin levels measured in the portal vein to the liver can range from 200 microU/ml* to 1,000 microU/ml immediately following a meal. Unfortunately, the insulin levels of type I diabetes patients on standard subcutaneous insulin therapy (either by syringe or using a typical insulin pump) can only reach a concentration of 15 microU/ml to 20 microU/ml at the portal vein. These lower insulin levels are insufficient to activate and maintain optimal hepatic glucose processing.  

In comparison, MAT^® treatment's high-dose insulin pulses imitate the body's own natural insulin release patterns and appear to enhance the liver's ability to store, mobilize and utilize glucose. The higher level of insulin available to the liver with the MAT^® procedure stimulates liver cells to synthesize glucokinase and probably other insulin-dependent enzymes. 

The chart below contrasts the two types of therapy and the levels of insulin available to the liver.

 

Two types of therapy in Type 1 diabetes
	MAT® treatment	Conventional Insulin Therapy
Insulin injection site	Directly into a vein	Subcutaneous tissue
Insulin reaches the liver	Rapidly	Slowly
Level of Insulin available to the liver.	Very High (200-1000 microU/ml)*	Very Low (15-20 microU/ml)*
Pattern of insulin delivery to the liver	Pulses - sharp spikes	Gradual rise and fall

* microU /ml = one millionth of a Unit of insulin per milliliter.

      First Phase

    MAT^®  insulin pulses also mimic the first phase of insulin secretion which has been shown to have a different effect on fuel metabolism than the basal oscillatory insulin secretion from the normal pancreas.

      Other tissues

    Because the insulin pulses are "seen" by the entire body, not just the liver, the MAT^® pulses may alter and improve the metabolism of all  organs.  In both normal and diabetic individuals, most organs rely on the metabolism of fatty acids for 70 percent to 80 percent of their fuel. However, the breakdown of fatty acids requires more oxygen at the cellular level than the breakdown of glucose for a given energy output. Pulsed insulin therapy may permit organs to use glucose as an energy source to a significantly greater extent than usual (due to increased pyruvate dehydrogenase activity) and thus decrease the organ's oxygen requirements.

   At times of reduced tissue oxygen, such as when circulation is decreased, chronic intermittent intravenous insulin (by enabling the production of energy from glucose) may permit heart, skeletal muscle, skin, and other organs to function more normally and even to repair damage and heal. 

 

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