Portal Insulin LLC
Formulations of approved insulin analogs for delivery through the portal circulation.
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Physiologic Insulin Action Insulin (a hormone made of protein) tells the body to reduce the amount of glucose (sugar) in the blood. Without insulin, blood sugar would remain high (a condition called "hyperglycemia). Chronic hyperglycemia leads to the long-term complications of diabetes. Extreme hyperglycemia causes diabetic ketoacidosis (DKA), which can be fatal.
In people with typical physiology, insulin is produced by the pancreas and released into the portal vein in response to the pancreas's detection of increased blood sugar. The portal vein delivers the insulin directly to the liver, which takes up 50-70% of the insulin. The remainder of the insulin flows to the rest of the body (through the "peripheral circulation") where it is taken up primarily by fat and muscle. Insulin causes the liver both to take-up circulating glucose and to stop releasing stored glucose into the body. The liver can absorb a high dose of insulin before it lowers blood sugar too much (a condition called "hypoglycemia," which can cause discomfort, coma, or even death in extreme cases). In contrast, insulin causes fat and muscle to take up large amounts of glucose, so it takes less insulin in the peripheral circulation to cause hypoglycemia. In addition, insulin-induced glucose uptake by fat can lead to weight gain. |
Insulin Action for
People Living with Diabetes A person whose pancreas makes no usable insulin has Type 1 Diabetes (T1D). These individuals must take insulin injections several times a day in order to remain healthy. For example, insulin must be injected at the start of the meal in order to counteract the spike in blood sugar that comes from digesting the meal.
Insulin injections today are made into the fat layer under the skin (or "subcutaneous"). Once injected, the insulin formulation forms a depot in the fat; this depot is absorbed into the blood over time. The amount of time for absorption depends on how the insulin was formulated. Even the fastest insulin formulations take several hours to absorb. Once absorbed from the fat, the insulin flows directly into the peripheral circulation. Because subcutaneously delivered insulin does not go directly to the liver, most of the dose remains in the periphery -- leading to higher than typical insulin levels and action in fat and muscle (a condition called "Peripheral Hyperinsulinemia"). Subcutaneously delivered insulin is associated with:
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Intraperitoneal Insulin
Insulin delivered directly into the peritoneal cavity (the peritoneum is a membrane that encloses a number of organs) overcomes many of the limitations of subcutaneously delivered insulin. Veins in this cavity drain into the portal vein, so insulin delivered into this cavity follows the same route as insulin released by the pancreas. In addition, the extensive vasculature in the cavity enables much faster absorption of insulin delivered here than is possible for subcutaneously delivered insulin.
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Benefits
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Challenges
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