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Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
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Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
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Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
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Isolation of Human Islets from Partially Pancreatectomized Patients
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Hyperinsulinaemia in cancer.

Emily J Gallagher1,2, Derek LeRoith3,4

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High insulin levels, common in obesity and diabetes, are linked to increased cancer risk and treatment resistance. Understanding insulin signaling in cancer is crucial for developing effective therapies.

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Area of Science:

  • Endocrinology
  • Oncology
  • Metabolic Syndrome

Background:

  • Elevated circulating insulin (hyperinsulinemia) is prevalent in obesity and type 2 diabetes due to insulin resistance in metabolic tissues.
  • Epidemiological studies link hyperinsulinemia to increased cancer risk and progression, positioning it as a key factor connecting obesity, diabetes, and cancer.
  • Insulin signaling is increasingly recognized as a mechanism of therapeutic resistance in targeted cancer therapies.

Purpose of the Study:

  • To elucidate the role of insulin and insulin receptor signaling in cancer progression.
  • To understand how cancer cells maintain insulin sensitivity despite systemic insulin resistance.
  • To inform the development of novel therapeutic strategies targeting insulin signaling in cancer.

Main Methods:

  • Review of recent advancements in understanding insulin receptor signaling pathways in cancer.
  • Analysis of epidemiological data associating hyperinsulinemia with cancer.
  • Examination of mechanisms underlying therapeutic resistance linked to insulin signaling.

Main Results:

  • Cancer cells can maintain insulin responsiveness even when other tissues are insulin-resistant.
  • Insulin receptor signaling pathways are critical in cancer cell proliferation and survival.
  • Hyperinsulinemia contributes to therapeutic failures in cancer treatment.

Conclusions:

  • Hyperinsulinemia is a significant factor linking metabolic disorders and cancer.
  • Targeting insulin signaling pathways presents a promising therapeutic avenue for cancer treatment.
  • Further research into insulin's role in cancer is essential given rising global obesity and diabetes rates.