HORMONE HIRIT – Intriguing Insulin
Patricia B. Gatbonton, MD, FPCp, FPSEM
Diabetes is an ancient disease. The Papyrus Ebers, an Egyptian document from 1550 B.C., describes its classic symptoms: frequent urination (polyuria), excessive thirst (polydipsia) and intense hunger (polyphagia), long before physicians put a name to the syndrome.
Diabetes comes from the Greek word meaning “siphon,” or “to go through,” mellitus is Latin for honey-sweet. Early physicians would taste their patient’s urine to confirm the diagnosis. Remedies ranged from various herbs and potions, astringents, leeching to carbohydrate restrictive diets.
Arateus of Cappadocia in the 2nd century describes the patient’s plight thus, “Patients never stop making water and the flow is incessant…Iife is short, unpleasant and painful, thirst unquenchable, drinking excessive … if for a while they abstain from drinking, their mouths become parched and their bodies dry; the viscera seems scorched up; the patients are affected by nausea, restlessness and a burning thirst, and within a short time, they expire.”
An ancient disease; but 21st century man, with computer brains and the latest technology, has yet to find a cure.
Medicine has come a long way though, since Frederick Banting and Charles Best discovered insulin in 1921. We may be no closer to a cure, but new drugs and designer insulins help lower blood sugar levels of persons with diabetes (PWD).
Sugar, sugar everywhere
How does diabetes come about?
Rice, bread, potatoes--any carbohydrate we eat–is broken down in our stomachs by digestive enzymes into glucose. This is sugar’s simplest form, the raw material that generates the body’s energy. Protein and fat are alternative glucose sources which are stored in muscle and fat tissue and mobilized when we are fasting.
Normally, after a meal, the sugar in our stomach triggers sensors that alert the pancreas, a small factory that lies behind the curve of the stomach. Special cells, the 11 -cells of the islets of Langerhans (which comprise 70 percent) synthesize, package and discharge stored insulin in two bursts, an immediate tall spike, followed by a second, smoother curve that releases insulin in a steady stream (but smaller amplitude) that brings down glucose levels to normal.
Ins and outs of Insulin
Insulin is a hormone, a chemical messenger made up of 51 amino acids or proteins in two chains (A and B) held together by chemical bonds that are first produced as pre-proinsulin and proinsulin. Splitting of proinsulin yields insulin and C-peptide, which clinicians can use to indirectly measure insulin secretion.
Insulin docks on insulin receptors on every cell in the body-affecting their function especially in insulin sensitive tissues: the liver, muscle and fat cells, which are responsible for energy storage-and sets off a complicated chain reaction that allows specific glucose transporters to pick up glucose waiting outside the cell doors. Imagine that insulin is the key that unlocks the door. Once inside the cell, glucose enters a process (remember the Kreb’s cycle?) that goes on in the mitochondria, the cell’s powerhouse that generates energy so our hearts can pump, so we can breathe, think, see, speak, live.
Normally, our body sources glucose in different ways. One way is from the food we eat. When we are not eating, in between meals or for longer stretches, when we are asleep through the night, the liver, the hub of glucose production, makes even more sugar from glycogen (glycogenolysis), its storage form.
Insulin also does the following:
• Inhibits new glucose production from liver glycogen and muscle protein
• Increases transport of glucose into fat and muscle
• Increase glycogen breakdown in fat and muscle (increasing glucose breakdown)
• Stimulation of glycogen synthesis
A state of insulin resistance results when insulin receptors are less responsive to the effect of insulin. Higher-than-normal amounts of insulin are necessary to maintain blood sugars at normal levels. In spite of the high levels of insulin, the insulin signal inside the cell is weak and fewer transporters travel to the cell wall to pick up the waiting glucose. Much less glucose enters the cell.
Because of insulin resistance, the pancreas works overtime to produce extra insulin. Initially, by increasing production by 150 percent or more, blood sugars remain normal. Unfortunately, the pancreas cannot keep this up for long, and the compensatory mechanism fails. Eventually, the β-cells are exhausted, insulin production drops and fasting blood glucose levels rise above 126 mg percent-the diagnostic cut off for diabetes.
This deficiency in β -cells insulin production together with a resistance to the effect of insulin in the body’s tissues, results in Type 2 diabetes mellitus.
The diabetic has sugar everywhere but the body cannot use it properly. In the midst of plenty the body starves for glucose.
Normally, our body sources glucose in different ways. One way is from the food we eat. When we are not eating, in between meals or for longer stretches, when we are asleep through the night, the liver, the hub of glucose production, makes even more sugar from glycogen (glycogenolysis), its storage form. It does this to support our brain which needs a certain amount of glucose each hour for its processes to work properly. Once its own stores have run out, the liver pulls out protein and fat stores and manufactures more sugar (gluconeogenesis). The problem is, all that extra sugar is useless and inflates the glucose levels further. It is a destructive cycle. Excess glucose is toxic to cells; it damages small and large arteries, oxidizes blood and lipids, leaks out in the urine, drawing water along with it causing frequent urination. Because the body wastes all its energy and cannot store any, the patient loses weight and has to eat voraciously to replenish himself.
By the time the full clinical spectrum of diabetes (frequent urination, extreme thirst and hunger) is manifest – some 10 to 15 years after the problem begins – the diabetic has numerous accompanying complications (hypertension, abnormal cholesterol levels, heart disease, kidney disease, etc).
The most important thing to understand is that almost all Type 2 diabetic patients will require insulin at some point because at diagnosis, β -cells cell reserve is approximately 50 percent. With each year of diabetes, especially if blood sugars remain persistently high, you lose an additional 4 percent per year. Do the math. If you are lucky to be alive by the 10th year of your diabetes, you will only be able to produce less than 10 percent of your insulin requirement. How quickly this process happens depends on how good your glucose control is. No matter what or how many oral medications you take, you cannot kick your pancreas’ production back up to normal.
The bottom line: Only insulin can replace insulin!
Next issue, we will tackle the types of insulin, insulin regimens and tips and techniques to inject insulin.
Metabolic actions of insulin on lipid and protein metabolism (from UptoDate 2008)
Inhibition of lipolysis in fat; decreased plasma fatty acid concentrations
Stimulation of fatty acid and triacylglycerol synthesis in fat and liver
Increased lipoprotein lipase activity in fat; increased triglyceride uptake into fat
Decreased fatty acid oxidation in muscle and liver
Increased rate of formation of very-low-density lipoproteins in liver
Increased transport of some amino acids into muscle, adipose tissue, liver and other cells
Increased rate of protein synthesis in muscle, adipose tissue, liver and other tissues
Decreased proteolysis in muscle
Decreased urea formation
Stayed tuned, and in good glucose control!
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