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Chapter: Basic & Clinical Pharmacology : Pancreatic Hormones & Antidiabetic Drugs

The Endocrine Pancreas

The endocrine pancreas in the adult human consists of approxi-mately 1 million islets of Langerhans interspersed throughout the pancreatic gland.


The endocrine pancreas in the adult human consists of approxi-mately 1 million islets of Langerhans interspersed throughout the pancreatic gland. Within the islets, at least four hormone-producing cells are present (Table 41–1). Their hormone products include insulin, the storage and anabolic hormone of the body; islet amy-loid polypeptide (IAPP, or amylin), which modulates appetite,gastric emptying, and glucagon and insulin secretion; glucagon, the hyperglycemic factor that mobilizes glycogen stores; somatostatin, a universal inhibitor of secretory cells; gastrin, which stimulates gastric acid secretion; and pancreatic peptide, a small protein that facilitates digestive processes by a mechanism not yet clarified.

Diabetes mellitus is defined as an elevated blood glucose asso-ciated with absent or inadequate pancreatic insulin secretion, with or without concurrent impairment of insulin action. The disease states underlying the diagnosis of diabetes mellitus are now classified into four categories: type 1, insulin-dependent diabetes; type 2,non–insulin-dependent diabetes; type 3, other; and type 4, gesta-tional diabetes mellitus (Expert Committee, 2003).

Type 1 Diabetes Mellitus

The hallmark of type 1 diabetes is selective beta cell (B cell) destruction and severe or absolute insulin deficiency. Type 1 diabetes is further subdivided into immune and idiopathic causes. The immune form is the most common form of type 1 diabetes. Although most patients are younger than 30 years of age at the time of diagnosis, the onset can occur at any age. Type 1 diabetes is found in all ethnic groups, but the highest incidence is in people from northern Europe and from Sardinia. Susceptibility appears to involve a multifactorial genetic linkage, but only 10–15% of patients have a positive family history.

For persons with type 1 diabetes, insulin replacement therapy is necessary to sustain life. Pharmacologic insulin is administered by injection into the subcutaneous tissue using a manual injection device or an insulin pump that continuously infuses insulin under the skin. 

Interruption of the insulin replacement therapy can be life-threatening and can result in diabetic ketoacidosis or death. Diabetic ketoacidosis is caused by insufficient or absent insulin and results from excess release of fatty acids and subsequent formation of toxic levels of ketoacids.

Type 2 Diabetes Mellitus

Type 2 diabetes is characterized by tissue resistance to the action of insulin combined with a relative deficiency in insulin secretion. A given individual may have more resistance or more beta-cell deficiency, and the abnormalities may be mild or severe. Although insulin is produced by the beta cells in these patients, it is inade-quate to overcome the resistance, and the blood glucose rises. The impaired insulin action also affects fat metabolism, resulting in increased free fatty acid flux and triglyceride levels and reciprocally low levels of high-density lipoprotein (HDL).

Individuals with type 2 diabetes may not require insulin to sur-vive, but 30% or more will benefit from insulin therapy to control blood glucose. It is likely that 10–20% of individuals in whom type 2 diabetes was initially diagnosed actually have both type 1 and type 2 or a slowly progressing type 1 called latent autoimmune diabetes of adults (LADA), and they ultimately require full insulin replace-ment. Although persons with type 2 diabetes ordinarily do not develop ketosis, ketoacidosis may occur as the result of stress such as infection or the use of medication that enhances resistance, eg, cor-ticosteroids. Dehydration in individuals with untreated or poorly controlled type 2 diabetes can lead to a life-threatening condition called nonketotic hyperosmolar coma. In this condition, the blood glucose may rise to 6–20 times the normal range and an altered mental state develops or the person loses consciousness. Urgent medical care and rehydration are required.

Type 3 Diabetes Mellitus

The type 3 designation refers to multiple other specific causes of an elevated blood glucose: pancreatectomy, pancreatitis, nonpancreatic diseases, drug therapy, etc. For a detailed list the reader is referred to the reference Expert Committee, 2003.

Type 4 Diabetes Mellitus

Gestational diabetes (GDM) is defined as any abnormality in glucose levels noted for the first time during pregnancy. Gestational diabetes is diagnosed in approximately 7% of all pregnancies in the USA. During pregnancy, the placenta and placental hormones create an insulin resistance that is most pronounced in the last trimester. Risk assessment for diabetes is suggested starting at the first prenatal visit. High-risk women should be screened immedi-ately. Screening may be deferred in lower-risk women until the 24th to 28th week of gestation.

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Basic & Clinical Pharmacology : Pancreatic Hormones & Antidiabetic Drugs : The Endocrine Pancreas |

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