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Related Concept Videos

Hypoglycemia and Glucagon01:15

Hypoglycemia and Glucagon

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...
Type II Diabetes II: Pathophysiology01:24

Type II Diabetes II: Pathophysiology

PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.
Hypoglycemia01:26

Hypoglycemia

Hypoglycemia is a blood glucose level below 70 mg/dL. It commonly occurs in individuals using insulin or insulin-secreting drugs, but may also arise in non-diabetic conditions. People with type 1 diabetes are at the highest risk because they depend on exogenous insulin. People with type 2 diabetes are also at risk, especially when treated with insulin or medications such as sulfonylureas, which increase insulin release regardless of blood glucose levels. It develops when insulin levels exceed...
Hyperglycemia01:29

Hyperglycemia

Hyperglycemia is an abnormally high blood glucose level. It is diagnosed by fasting glucose ≥126 mg/dL, 2-hour oral glucose tolerance test (or OGTT) ≥200 mg/dL, random glucose ≥200 mg/dL with symptoms, or HbA1c ≥6.5%. However, HbA1c results may be unreliable in certain conditions, such as anemia or hemoglobinopathies, and the diagnosis should be confirmed unless classic symptoms are present. Postprandial hyperglycemia is typically considered significant when glucose levels exceed 180 mg/dL two...
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

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.
In addition to accelerating glucose uptake and utilization, insulin has...
Glucose Homeostasis: Regulation of Blood Glucose01:02

Glucose Homeostasis: Regulation of Blood Glucose

Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...

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Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
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Published on: November 16, 2011

Recurrent hypoglycemia increases hypothalamic glucose phosphorylation activity in rats.

Mayowa A Osundiji1, Paul Hurst, Stephen P Moore

  • 1Department of Medicine and Institute of Metabolic Science, University of Cambridge, Addenbrookes Hospital, Cambridge, UK.

Metabolism: Clinical and Experimental
|July 30, 2010
PubMed
Summary

Recurrent hypoglycemia increases hypothalamic glucose phosphorylation in rats, potentially impairing the body's defense against low blood sugar. This adaptation may explain counterregulatory failure in diabetes.

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Published on: January 4, 2018

Area of Science:

  • Neuroendocrinology
  • Metabolic Regulation
  • Diabetes Complications

Background:

  • Impaired counterregulatory responses to hypoglycemia in diabetes are not fully understood.
  • Previous theories focused on glucose delivery to the hypothalamus, but evidence is inconclusive.

Purpose of the Study:

  • To investigate if increased hypothalamic glucose phosphorylation, not glucose delivery, underlies impaired counterregulation after recurrent hypoglycemia.
  • To test the hypothesis that this metabolic adaptation preserves glucose flux, reducing hypoglycemia detection.

Main Methods:

  • A rat model of recurrent insulin-induced hypoglycemia was established.
  • Hypothalamic glucose phosphorylation activity was measured over 4 days of hypoglycemia.
  • Epinephrine responses were monitored as a key counterregulatory hormone.

Main Results:

  • Recurrent hypoglycemia progressively suppressed epinephrine responses.
  • Hypothalamic glucose phosphorylation significantly increased in a day-dependent manner (2.8-fold by day 4).
  • No changes in glucose phosphorylation were observed in the brain stem or frontal cortex.

Conclusions:

  • The hypothalamus adapts to recurrent hypoglycemia by increasing glucose phosphorylation.
  • This adaptation may contribute to the failure of counterregulatory responses during hypoglycemia.
  • Findings suggest a novel mechanism for hypoglycemia unawareness in diabetes.