Insulin regulation of blood glucose



Insulin regulation of blood glucose

Action of glucose:

Insulin is an endocrine hormone secreted by the beta cells of the islets of Langerhans in the pancreas. Its principal function is to induce the transport of glucose across cellular membranes (primarily liver, skeletal muscle and adipose tissue), leading to a decrease in blood sugar. When insulin is lacking or if the body cannot respond to it, only a small amount of glucose can cross cell membranes and be used in cellular metabolism. This low rate of cellular glucose uptake results in excess accumulation of glucose in the blood or hyperglycemia. An excess of insulin results in the opposite condition, hypoglycemia (low blood sugar), by inducing an excessive amount of glucose uptake, thus lowering blood glucose concentrations. The normal concentration for blood glucose in around 90 mg% (or 90 mg per 100 ml of blood) but it may range from 60 mg% to 140 mg%, depending on an individual’s dietary intake of glucose.

The disease diabetes mellitus can be caused by either a lack of insulin (Type I diabetes, insulin-dependent diabetes or “juvenile” onset) or a lack of a response to insulin (Type II diabetes, insulin-independent diabetes or “adult” onset). Type I diabetics often have an autoimmune disorder that selectively targets their pancreatic beta cells for destruction by their own antibodies, leading to the symptoms typical of diabetes: high blood glucose levels and excretion of glucose in the urine. Similar symptoms occur in Type II diabetes or insulin-independent diabetes. Here, the body is capable of producing insulin, and blood insulin concentrations are often elevated, but insulin does not produce the typical uptake of glucose into muscle and liver because the cells have become resistance to insulin, leading to hyperglycemia. In both cases, urinary excretion of glucose (glucosuria) results when the concentration of glucose in the plasma exceeds the threshold level (Tmax) for glucose reabsorption by the proximal tubule of the nephron (which occurs when all glucose transporters within the proximal tubules are working at their maximal rate). The increased osmolarity of the tubular fluid (due to the remaining glucose in the filtrate) relative to that of the interstitial fluid reduces water reabsorption and causes abnormally large amounts of water to be excreted (polyuria). The increase in water excretion (diuresis) may lead to dehydration, which in turn stimulates excessive water intake by drinking (polydipsia). Glucosuria, polyuria, and polydipsia are three major characteristics of diabetes.

When insulin is deficient and the cells cannot metabolize glucose for energy, the cells compensate by increasing their metabolism of fat and proteins. The increased metabolism of fats releases large quantities of ketone bodies (i.e., acetone) into the blood; ketone bodies are intermediate products of fat metabolism. The ketones are excreted in the urine and have an easily recognizable odor of acetone (also true of a diabetics breath). Additionally, ketone bodies are acidic and their accumulation will cause a decrease in extracellular fluid (including blood) pH, leading to an acidosis. Severe acidosis may lead to coma and eventually death.

Glucose tolerance test

In diagnosing diabetes, several tests are used to determine as precisely as possible what metabolic error is causing the disease. Tests include determining the concentrations of urinary glucose, urinary ketone bodies, fasting blood glucose levels, insulin sensitivity and the glucose tolerance test, the latter of which we will do in lab.

The glucose tolerance test assays the ability of the body (particularly the pancreas) to respond to ingestion of excess amounts of glucose. The changes in blood glucose following the ingestion of 1 g glucose per 1 kg body mass are markedly different between normal individuals and diabetics (fig. 1). In a normal individual, blood glucose rises from approximately 90mg% to around 140 mg% within one hour and then falls back to normal within three hours; blood glucose may actually fall lower than initial readings due to the excess amount of insulin secreted by the pancreas in response to the glucose challenge.

The diabetic person shows a hyperglycemic

response in which the blood glucose rises from around 140 mg% to as high as 300 mg% and then slowly falls to the fasting (elevated) level after 5-6 hours. The diabetics abnormal response is caused by the inability of the pancreas to secrete additional insulin in response to the elevated blood glucose levels.

Experimental procedure

1. At least one individual from every group should volunteer. More than one individual per group may choose to do the assay. If you are planning on being a subject, please carefully read the following before lab and be ready to rapidly come into the lab, do your initial test and then drink your glucose solution.

2. You should report to lab in a (semi) fasted state. Ideally you should not have eaten for the last 12-18 hrs (which is one of the reasons why glucose tolerance tests are usually performed first thing in the morning – the other is that glucose tolerance exhibits a diurnal rhythm, with a lower tolerance in the afternoon).

3. Estimate your mass in kg (Conversion factor: 1 lb = 0.454 kg) and then drink one of the flavored glucose solutions so that you are ingesting 1 g glucose/dextrose per 1 kg body mass, upto a maximum of 75 g glucose ingested. The solutions either contain 7 g glucose per oz. (cola flavored) or 10 g glucose per oz. (orange flavored). This should be done within 15 min of coming to lab.

4. Determine your resting (normal) blood glucose level using the glucose meter in the lab immediately after drinking the glucose drink (we don’t want to allow time for the glucose to enter your blood stream). Obtain blood for the test from a finger using a sterile lancet (use proper blood handling techniques). Clean the finger with an alcohol wipe prior to taking the sample. Additionally, take a urine Labstix text strip to the rest room and test your urine for the presence of glucose (you do not need to bring back a sample) following the directions on the container. Record your values on the class data sheet on the computer and on the whiteboard.

5. After ingesting the glucose, repeat the blood test every 30 minutes until the end of the lab period. Additionally, test another urine sample for each blood sample (or until you have had at least one negative result after your peak blood glucose sample).

6. Continue to record your data on both the computer spread sheet and the blackboard. How do your results compare with the normal glucose tolerance test curve shown in fig. 1?

|1999 WHO Diabetes criteria - Interpretation of Oral Glucose Tolerance Test |

|Glucose levels |NORMAL |impaired fasting glycaemia (IFG) |impaired glucose tolerance (IGT) |Diabetes Mellitus (DM) |

Venous Plasma |Fasting |2hrs |Fasting |2hrs |Fasting |2hrs |Fasting |2hrs | |(mg/dl) | ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download