Endocrine Pancreas and Type 1 Diabetes

Endocrine Pancreas

• Composed of clusters of cells called islets of Langerhans
• Each islet contains multiple cell types, each producing a unique hormone
• Insulin is produced by beta cells, located centrally within the islets
• Insulin is a major anabolic hormone, increasing glucose uptake by skeletal muscle and adipose tissue, reducing serum glucose
• Increased glucose uptake leads to glycogen, protein, and lipid synthesis
• Glucagon is produced by alpha cells, acting in opposition to insulin, increasing blood glucose levels during fasting (via glycogenolysis and lipolysis)

Type 1 Diabetes Mellitus

• Characterized by insulin deficiency due to autoimmune destruction of beta cells
• Often caused by T lymphocytes
• Inflammation of islets is common
• Associated with HLA-DR3 and HLA-DR4
• Autoantibodies against insulin are often present years before clinical diagnosis
• Initial symptoms appear in childhood
• High blood glucose, reduced glucose uptake by fat and skeletal muscle due to lack of insulin
• Hyperglycemia is a key characteristic

Type 2 Diabetes Mellitus

• Predominantly an end-organ insulin resistance disorder
• Characterized by hyperglycemia
• Accounts for 90% of diabetes cases, most prevalent in middle-aged obese adults.
• Obesity is linked to decreased insulin receptors
• High genetic predisposition
• Early in the disease, insulin levels may be elevated, but later, beta cell exhaustion leads to insulin deficiency
• Often clinically silent in early stages; polyuria, polydipsia, and hyperglycemia are common clinical features
• Diagnosis based on random glucose levels exceeding 200 mg/dL, fasting glucose over 126 mg/dL or glucose tolerance test showing over 200 mg/dL two hours after glucose consumption

Long-Term Consequences of Diabetes

• Nonenzymatic glycosylation (NEG) of vascular basement membranes leads to atherosclerosis, cardiovascular disease, and peripheral vascular disease.
• NEG of small vessels leads to hyaline arteriolosclerosis, affecting kidneys and resulting in small scarred kidneys.
• NEG of hemoglobin forms glycated hemoglobin (HbA1c), a marker of blood glucose control.
• Osmotic damage occurs as glucose enters Schwann cells, pericytes, and lens; this leads to nerve damage, blindness, and cataracts.

Pancreatic Endocrine Neoplasms

• Tumors of islet cells, a relatively rare component of pancreatic neoplasms (<5% of pancreatic tumors)
• Often associated with MEN-1 syndrome, alongside parathyroid hyperplasia and pituitary adenomas
• Insulinomas are characterized by episodic hypoglycemia, relieved by glucose administration
• Gastrinomas cause treatment-resistant peptic ulcers (Zollinger-Ellison syndrome)
• Somatostatinomas result in achlorhydria and cholelithiasis with steatorrhea
• VIPomas manifest as watery diarrhea, hypokalemia, and achlorhydria.