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INTRODUCTION

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In the endocrine pancreas, the islets of Langerhans contain at least 4 types of endocrine cells, including A (alpha, glucagon producing), B (beta, insulin, and amylin producing), D (delta, somatostatin producing), and F (pancreatic polypeptide producing). Of these, the B (insulin-producing) cells are the most numerous.

The most common pancreatic disease requiring pharmacologic therapy is diabetes mellitus, a deficiency of insulin production or effect. Diabetes is treated with several parenteral formulations of insulin and oral or parenteral noninsulin antidiabetic agents. Glucagon, a hormone that affects the liver, cardiovascular system, and gastrointestinal tract, can be used to treat severe hypoglycemia.

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DIABETES MELLITUS

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Diabetes mellitus is classified into four categories: type 1, type 2, other, and gestational diabetes mellitus. Here, we focus on type 1 and type 2. Type 1 diabetes usually has its onset during childhood and results from autoimmune destruction of pancreatic B cells. Type 2 diabetes is a progressive disorder characterized by increasing insulin resistance and diminishing insulin secretory capacity. Type 2 diabetes is frequently associated with obesity and is much more common than type 1 diabetes. Although type 2 diabetes usually has its onset in adulthood, the incidence in children and adolescents is rising dramatically, in parallel with the increase in obesity in children and adolescents.

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High-Yield Terms to Learn
Alpha-glucosidase An enzyme in the gastrointestinal tract that converts complex starches and oligosaccharides to monosaccharides; inhibited by acarbose and miglitol
Beta (B) cells in the islets of Langerhans Insulin-producing cells in the endocrine pancreas
Hypoglycemia Dangerously lowered serum glucose concentration; a toxic effect of high insulin concentrations and the secretagogue class of oral antidiabetic drugs
Lactic acidosis Acidemia due to excess serum lactic acid; can result from excess production or decreased metabolism of lactic acid
Type 1 diabetes mellitus A form of chronic hyperglycemia caused by immunologic destruction of pancreatic beta cells
Type 2 diabetes mellitus A form of chronic hyperglycemia initially caused by resistance to insulin; often progresses to insulin deficiency

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The clinical history and course of these 2 forms differ considerably, but treatment in both cases requires careful attention to diet, fasting and postprandial blood glucose concentrations, and serum concentrations of hemoglobin A1c, a glycosylated hemoglobin that serves as a marker of glycemia. Type 1 diabetes requires treatment with insulin. The early stages of type 2 diabetes usually can be controlled with noninsulin antidiabetic drugs. However, patients in the later stages of type 2 diabetes often require the addition of insulin to their drug regimen.

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INSULIN

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A. Physiology
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Insulin is synthesized as the prohormone proinsulin, an 86-amino-acid single-chain polypeptide. Cleavage of proinsulin and cross-linking result in the 2-chain 51-peptide insulin molecule and a 31-amino-acid residual C-peptide. Neither proinsulin nor C-peptide appears to have any physiologic actions.

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