Treatment of type 1 diabetes
02 January 2021 18:03
Normal blood glucose and insulin 24 hours profiles
When lean and obese non-diabetic individuals were given meal containing glucose, there is a
substantial difference in insulin concentration required to achieve the glucose values between the
lean and obese individuals, even though the glucose levels are very similar.
Normal blood insulin concentration
Insulin secretion rapidly changes by order of magnitude or more. Low level secretion persists during
fasting. Prandial (after eating) insulin secretion is proportionate to requirements.
Insulin exists in its natural sequence form as hexamers packaged around zinc in the centre. Before
insulin can diffuse in and out of capillaries to flow around the body, it needs to break down.
So, the zinc ions diffuses away and the hexamers breaks down into dimers and then separate into
monomers.
Only insulin monomers are able to cross into blood and circulate around the blood and diffuse out
and bind to insulin receptor.
Endogenous insulin secretion enters the liver directly
Beta cells are in the islets of the pancreas. Pancreas are closely opposed to capillaries that drain into
the hepatic portal vein. When beta cells secrete insulin, the insulin hexamer rapidly falls apart into
dimers ----> monomers. The monomers are then taken up into the blood and they travel through the
hepatic portal vein directly into the liver.
This is really important because the liver is where insulin has its most important effect in terms of
reducing gluconeogenesis and glycogenolysis. This allows the glucose to be taken up by the body for
energy after meals.
After having the effect on the liver, it passes from the hepatic portal system into the hepatic vein
then to the heart. The insulin then gets pumped around the lungs and the right sided circulation, the
pulmonary circulation and then it's pumped around rest of the body.
The insulin becomes diluted during the process and some of it gets cleared.
After blood that has been through this process of dilution and some has been cleared, only then
insulin concentration in the peripheral blood is measured.
Exogenous insulin is diluted before entering target organs
Exogenous insulin is administered into the subcutaneous space by injection. It drains the capillaries
of a subcutaneous adipose tissue into the systemic circulation. That in turn drains into the heart in
the right ventricle, which then pumps it around the pulmonary circulation. The insulin then gets
transported to the whole body. After further dilution and clearing via kidneys, the insulin comes into
contact with liver, muscles, adipose tissue, which are the areas where glucose is taken up and come
into contact with insulin.
Non-target organs also get exposed to exogenous insulin and only after transport to the whole body,
exogenous insulin concentration in peripheral blood is measured.
In type 1 diabetes, mimicking normal insulin secretion is difficult
If insulin is swallowed, proteases in the stomach will rapidly break it down and almost none of the
insulin will get through the circulation. So insulin must be injected into individuals.
Excess insulin injection can result in hypoglycaemia after eating. Due to the challenges of balancing
insulin injection after a meal, number of different insulin have been developed over the years. For
example:
• Rapid-acting analogues: comes closest to mimicking the prandial release of endogenous
Treatment - Diabetes Page 1
02 January 2021 18:03
Normal blood glucose and insulin 24 hours profiles
When lean and obese non-diabetic individuals were given meal containing glucose, there is a
substantial difference in insulin concentration required to achieve the glucose values between the
lean and obese individuals, even though the glucose levels are very similar.
Normal blood insulin concentration
Insulin secretion rapidly changes by order of magnitude or more. Low level secretion persists during
fasting. Prandial (after eating) insulin secretion is proportionate to requirements.
Insulin exists in its natural sequence form as hexamers packaged around zinc in the centre. Before
insulin can diffuse in and out of capillaries to flow around the body, it needs to break down.
So, the zinc ions diffuses away and the hexamers breaks down into dimers and then separate into
monomers.
Only insulin monomers are able to cross into blood and circulate around the blood and diffuse out
and bind to insulin receptor.
Endogenous insulin secretion enters the liver directly
Beta cells are in the islets of the pancreas. Pancreas are closely opposed to capillaries that drain into
the hepatic portal vein. When beta cells secrete insulin, the insulin hexamer rapidly falls apart into
dimers ----> monomers. The monomers are then taken up into the blood and they travel through the
hepatic portal vein directly into the liver.
This is really important because the liver is where insulin has its most important effect in terms of
reducing gluconeogenesis and glycogenolysis. This allows the glucose to be taken up by the body for
energy after meals.
After having the effect on the liver, it passes from the hepatic portal system into the hepatic vein
then to the heart. The insulin then gets pumped around the lungs and the right sided circulation, the
pulmonary circulation and then it's pumped around rest of the body.
The insulin becomes diluted during the process and some of it gets cleared.
After blood that has been through this process of dilution and some has been cleared, only then
insulin concentration in the peripheral blood is measured.
Exogenous insulin is diluted before entering target organs
Exogenous insulin is administered into the subcutaneous space by injection. It drains the capillaries
of a subcutaneous adipose tissue into the systemic circulation. That in turn drains into the heart in
the right ventricle, which then pumps it around the pulmonary circulation. The insulin then gets
transported to the whole body. After further dilution and clearing via kidneys, the insulin comes into
contact with liver, muscles, adipose tissue, which are the areas where glucose is taken up and come
into contact with insulin.
Non-target organs also get exposed to exogenous insulin and only after transport to the whole body,
exogenous insulin concentration in peripheral blood is measured.
In type 1 diabetes, mimicking normal insulin secretion is difficult
If insulin is swallowed, proteases in the stomach will rapidly break it down and almost none of the
insulin will get through the circulation. So insulin must be injected into individuals.
Excess insulin injection can result in hypoglycaemia after eating. Due to the challenges of balancing
insulin injection after a meal, number of different insulin have been developed over the years. For
example:
• Rapid-acting analogues: comes closest to mimicking the prandial release of endogenous
Treatment - Diabetes Page 1
