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. 2010 Oct;59(10):2333-9.
doi: 10.2337/db10-0103.

Hypoglycemia in type 1 diabetes

Rory J McCrimmon  1 , Robert S Sherwin
Affiliations

Hypoglycemia in type 1 diabetes

Rory J McCrimmon et al. Diabetes. 2010 Oct.
No abstract available

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Figures

FIG. 1.
FIG. 1.
Integrative model of hypoglycemia detection. A falling glucose is detected by peripheral and central glucose-sensing cells/neurons. Peripheral glucose sensors signal back to glucose-sensing regions of the hindbrain in turn activating efferent pathways that initiate a counterregulatory response. At the same time, glucose sensors in the hypothalamus, such as those in the VMH and other forebrain regions, detect falling glucose, also activating efferent pathways that initiate a counterregulatory response. Integrative pathways between hindbrain, hypothalamic, and other forebrain regions are reciprocally connected and can modulate responses to the hypoglycemic signal. Glucose-sensing regions in the brain, such as the VMH, contain GE and GI neurons and an astrocytic support structure. A, astrocytic.
FIG. 2.
FIG. 2.
A simplified model of glucose-sensing mechanisms present in the brain. Glucose from the arterial supply is transported either directly into neurons via GLUT-3 (possibly GLUT-2) or indirectly as lactate generated through glycolysis in astrocytes. Glucose is phosphorylated by GK, a key regulatory step in glucose sensing, before undergoing oxidative-phosphorylation to generate ATP. ATP closes the SUR-1–selective KATP, leading to membrane depolarization, calcium influx, and release of neurotransmitters and/or neuropeptides. In addition, AMP-to-ATP ratios are monitored by AMPK, activation that during hypoglycemia stimulates the production of nitric oxide and may act via the KATP channel or directly to stimulate neurotransmitter release. Additional mechanisms that may modulate this basic glucose-sensing mechanism include: 1) SGLTs, 2) GABAergic inhibition (or modulation by other neurotransmitters such as norepinephrine), and 3) the actions of hormones such as insulin and leptin and neuropeptides such as urocortin 3. CI−, chloride; Ins, insulin; MCT, monocarboxylate transporters; NOS, nitric oxide synthase; UCN3, urocortin 3.
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