Diabetes Mellitus:- Part 1 – Carbohydrate and Glucose Metabolism, Insulin and Glucagon

Carbohydrate and Glucose Metabolism

This test can be done on serum. The serum should be separated within 30 minutes of collection.
The Serum can be stored at 25° C for 8 hours and 72 hours at 4 °C.
Oxalate blood can also be used. Preservative sodium fluoride may be added.
The plasma can be stored at 25 °C for 24 hours (with preservative sodium fluoride).

Carbohydrates are major components of the diet and are an important energy source.
1. Glucose is controlled by insulin and glucagon.
2. Glucose is low in the fasting state.
3. The glucose = C₆H₁₂O₆ = C₆ (H₂O)6.
4. Lactose = C₁₂H₂₂O₁₁ = C₁₂ (H₂O)_11.
The capacity of the body to store the carbohydrate is limited:
1. The liver can store only 10% of its wet weight.
2. Muscles can store 5% of their wet weight.
3. This store amount is only sufficient for half a day.
Carbohydrates include sugar and starch.
1. The salivary gland enzyme converts starch and glycogen into dextrin and maltose.
  1. The acid pH of the stomach inhibits salivary amylase.
  2. Pancreatic alkaline secretion of amylase acts mainly on maltose and the disaccharides.
  3. Maltose, lactose, and sucrose are converted into:
    1. Glucose.
    2. Galactose.
    3. Fructose.

The functions of the carbohydrates are:

Glucose Metabolism:

Glucose is formed by the breakdown of :

Grains.
Starchy vegetables.
Legumes.
Body store of glycogen.
Endogenous proteins.
Excess glucose is converted into fat by adipose cells and stored in the adipose tissue.
Possible Glucose metabolic pathways
The Triose pathway is the main junction where four pathways intersect and help to maintain the glucose level.
1. This is a complicated enzymatic system, but the glucose level is maintained in the normal range.
  Glucose metabolism
Glucose metabolism is interlinked with fats and proteins, as shown in the two diagrams.
Glucose levels are controlled by insulin and glucagon.
Insulin and glucagon role in glucose metabolism

Glucose metabolism and role of liver

Carbohydrate metabolism

Glucagon is produced by the Alpha (α) cells of islets of Langerhans in the pancreas.
Glucose level is regulated by insulin and glucagon
It is 29 amino acids polypeptide.
The major target organ is the liver, which binds to a specific receptor and increases intracellular adenosine-5-monophosphate and calcium.
Glucagon stimulates the production of glucose in the liver by glycogenolysis and gluconeogenesis.
It also increases ketogenesis in the liver.
Minor target organ is fat where it causes lipolysis.
Glucagon secretion is controlled by glucose level.
1. A low glucose level is stimulatory.
2. A high glucose level is inhibitory.
In the case of fasting, protein and fats are broken down into glucose under the influence of Glucagon.
In the case of long-standing diabetes mellitus impairs the glucagon response to hypoglycemia, leading to increased chances for hypoglycemia episodes.
Insulin inhibits glucagon secretion from the pancreas.

Insulin is produced by the beta cells of islets of Langerhans in the pancreas.
1. Insulin is an anabolic hormone.
2. First, proinsulin is formed in ribosomes of the rough endoplasmic reticulum.
3. Later on, stored in the Golgi apparatus.
4. Proteolytic cleavage from Insulin and C-peptide.
  Insulin formation
Diabetes mellitus results from the abnormality in the production or use of insulin.
1. β-cells of the pancreas produce insulin, and the involvement of these Β-cells abnormality leads to diabetes mellitus:
  1. β-cells insulin production is deficient.
  2. Normal synthesis but abnormal release.
  3. Extra-pancreatic factors are like peripheral tissue cells receptor dysfunction, producing resistance to the cellular action of insulin.
  4. Non-pancreatic hormones will affect insulin secretion or blood glucose metabolism.
2. C-peptide has no biological activity and has a long life than insulin.
  1. Fasting C-peptide concentration is 5 folds to 10 folds higher than the insulin.
    C-peptide and Proinsulin characteristic features
Insulin action:
1. Insulin attaches to the insulin receptors on muscles, liver, and fatty cells.
2. It pushes the glucose into the cells to be metabolized to glycogen, amino acid, and fatty acids.
  Glucose and insulin receptor role
3. Insulin lowers the plasma glucose level.
  Insulin functions
Increased insulin will lower the blood glucose level, and deficiency will increase glucose.
Insulin and glucagon functions

Insulin and glucagon role in glucose metabolism

Other hormones like Adreno-corticosteroids, ACTH, epinephrine, thyroxine can affect glucose metabolism.
1. The above hormones increase the plasma glucose level.
Serum glucose level is dependant upon the time and relation to food intake.
The glucose level is low in the fasting state.
1. Glucose goes to the normal state after 2 hours of food intake.
The concentration of glucose is higher in arterial blood than venous.
When fasting glucose is around 126 mg/dl, try to estimate glucose level after oral 75 grams of glucose.
1. Now check one-hour and two-hour samples.
2. This oral glucose test will pick up Impaired Glucose Tolerance cases, where you can prevent the development of Diabetes Mellitus.
3. The fasting level is between 100 to 126 mg/dl, which is called fasting hyperglycemia.
4. The glucose level of 135 mg/dL is abnormal in the fasting state but is normal after one hour of meal.

Lab findings in hyperglycemia (Diabetes mellitus)