Insulin is the principal hormone responsible for the control of glucose metabolism. It is synthesized in the b cells of the islets of Langerhans as the precursor, proinsulin, which is processed to form C-peptide and insulin, and both are secreted in equimolar amounts into the portal circulation. The mature insulin molecule comprises two polypeptide chains, the A chain (21 amino acids) and the B chain (30 amino acids), which are linked by two inter-chain disulphide bridges. There is, in addition, a single intra-chain disulphide bridge in the A chain. The sequence of insulin is highly conserved in mammalian species, and is homologous with the insulin-like growth factors IGF-I and IGF-II.

Secretion of insulin is mainly controlled by plasma glucose concentration and the hormone has a number of important metabolic actions. Its principal function is to control the uptake and utilization of glucose in peripheral tissues via the glucose transporter. This and other hypoglycemic activities, such as the inhibition of hepatic gluconeogenesis and glycogenolysis are counteracted by the hyperglycemic hormones including glucagon, epinephrine (adrenaline), growth hormone and cortisol. Insulin concentrations are severely reduced in type 1 diabetes and some other conditions such as hypopituitarism. Insulin concentrations may be raised in type 2 diabetes, obesity, insulinoma and some endocrine dysfunctions such as Cushing's syndrome and acromegaly.

The main clinical utility of insulin measurement is the investigation of hypoglycemia. Insulin assays have been used in the following applications:

1. To assess the residual (I cell function, especially in newly diagnosed cases of type 1 diabetes.
   
   
2. As an aid to the discrimination between types 1 and 2 diabetes.
   
   
3. The diagnosis of insulinoma.
   
   
4. The investigation of the pathophysiology of diabetes mellitus. Insulin assays are essential in various dynamic tests, such as oral or intravenous glucose tolerance tests (OGTT and IVGTT), to determine the insulin response of the pancreas and the degree of insulin resistance.

In many applications, insulin measurements may be complicated by cross-reactivity with partially degraded insulin, proinsulin and split forms of proinsulin. Immune complexes of these molecules are especially problematic in patients who have developed anti-insulin antibodies through animal insulin administration.

C-peptide is a single chain of 31 amino acids (MW 3020), connecting the A and B chains of insulin in the proinsulin molecule. Unlike insulin, C-peptide has no known physiological function. Because C-peptide has a longer half-life than insulin (2-5 times longer), higher concentrations of C-peptide persist in the peripheral circulation, and these levels fluctuate less than insulin. For these reasons, plasma C-peptide concentrations may reflect pancreatic insulin secretion more reliably than the level of insulin itself. C-peptide is cleared from the body by the kidney, and, unlike insulin, urine concentrations are 20 - 50 times higher than in plasma. Unlike plasma insulin levels, which fluctuate in response to meals, measurement of the 24-hour urinary excretion of C-peptide provides a useful monitor of average b cell insulin secretion. C-peptide measurement is used for the following clinical applications:

1. To assess the residual b cell function in patients treated with insulin and to distinguish between types 1 and 2 diabetes. Of particular interest is its use to indicate the need for progression to insulin therapy in type 2 diabetes.
   
   
2. The diagnosis of factitious hypoglycemia. The surreptitious administration of insulin causes high insulin levels in the absence of elevated C-peptide concentrations.
   
   
3. Insulinoma diagnosis, especially in patients treated with insulin. C-peptide measurement is used in insulin suppression tests in euglycemic patients with suspected insulinoma. Elevated C-peptide levels in this test are indicative of insulinoma.
   
   
4. As a marker for residual pancreatic tissue after pancreatectomy. In the case of insulinoma, C-peptide measurement may be used to detect metastasis and the response to therapy. It may also be used to monitor the progress of pancreas or islet cell transplantation.

AutoDELFIA diagnostic kits for insulin and C-peptide are based on the same proven DELFIA chemistry as our research assays for diabetes.The analytical sensitivity of the AutoDELFIA Insulin assay is typically better than 0.5 mU/mL (3 pmol/L). The analytical sensitivity of the AutoDELFIA C-peptide assay is typically better than 0.015 ng/mL (4.97 pmol/L).

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