Leptin acts in the brain to influence hypoglycemic counterregulation: disparate effects of acute and recurrent hypoglycemia on glucagon release

Leptin has been shown to diminish hyperglycemia via reduced glucagon secretion, although it can also enhance sympathoadrenal responses. However, whether leptin can also inhibit glucagon secretion during insulin-induced hypoglycemia or increase epinephrine during acute or recurrent hypoglycemia has not been examined. To test whether leptin acts in the brain to influence counterregulation, hyperinsulinemic hypoglycemic (∼45 mg/dl) clamps were performed on rats exposed to or not exposed to recurrent hypoglycemia (3 days, ∼40 mg/dl). Intracerebroventricular artificial cerebral spinal fluid or leptin was infused during the clamp. During acute hypoglycemia, leptin decreased glucagon responses by 51% but increased epinephrine and norepinephrine by 24 and 48%, respectively. After recurrent hypoglycemia, basal plasma leptin levels were undetectable. Subsequent brain leptin infusion during hypoglycemia paradoxically increased glucagon by 45% as well as epinephrine by 19%. In conclusion, leptin acts within the brain to diminish glucagon secretion during acute hypoglycemia but increases epinephrine, potentially limiting its detrimental effects during hypoglycemia. Exposure to recurrent hypoglycemia markedly suppresses plasma leptin, whereas exogenous brain leptin delivery enhances both glucagon and epinephrine release to subsequent hypoglycemia. These data suggest that recurrent hypoglycemia may diminish counterregulatory responses in part by reducing brain leptin action.

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Cerebral glycogen in humans following acute and recurrent hypoglycemia: Implications on a role in hypoglycemia unawareness

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16678240 ◽

2016 ◽

Vol 37 (8) ◽

pp. 2883-2893 ◽

Cited By ~ 15

Author(s):

Gülin Öz ◽

Mauro DiNuzzo ◽

Anjali Kumar ◽

Amir Moheet ◽

Ameer Khowaja ◽

...

Keyword(s):

Occipital Lobe ◽

Biophysical Model ◽

Resonance Spectroscopy ◽

Hypoglycemic Episode ◽

Hypoglycemia Unawareness ◽

Brain Glycogen ◽

Acute Hypoglycemia ◽

The Brain ◽

Recurrent Hypoglycemia

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-13C]glucose intravenously over 80+ h while maintaining euglycemia. 13C-glycogen levels in the occipital lobe were measured by 13C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior 13C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.

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Opportunistic Disease or Metastatic Lesions: A Rare Finding in a Patient with Bladder Cancer

Current Urology ◽

10.1159/000499293 ◽

2019 ◽

Vol 13 (1) ◽

pp. 54-56

Author(s):

Michael Simon ◽

Natalie Elkayam ◽

Jonathan Smerling ◽

Michael Marcelin ◽

Stephan Kamholz

Keyword(s):

Bladder Cancer ◽

Metastatic Disease ◽

Cerebral Spinal Fluid ◽

Vasogenic Edema ◽

Brain Biopsy ◽

Spinal Fluid ◽

Cd4 Count ◽

Frontal Horn ◽

The Right ◽

The Brain

A 66-year-old male with a history of human immunodeficiency virus infection and metastatic bladder cancer presented to our hospital for a further workup of a focal seizure involving the patients left upper extremity. The patient was undergoing active chemotherapy at the time of admission and had a CD4 count of 111. Magnetic resonance imaging of the brain revealed multiple ring-enhancing lesions in the right frontal lobe associated with vasogenic edema, and mass effect at the right frontal horn of the lateral ventricles. As the imaging was not consistent with typical metastatic disease of the bladder, further testing was performed. A lumbar puncture was performed to assist in differentiating between malignant and infectious causes in the setting of a low CD4 count. The cerebral spinal fluid was sterile and no malignant cells were identified. Protein and glucose levels of the cerebral spinal fluid were within normal range. To confirm the presence of metastatic disease, a brain biopsy was performed and found to be consistent with metastatic carcinoma with a bladder primary. The patient subsequently underwent radiation therapy to the site of the brain metastasis.

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Effects of Anisotonicity in the Cisterna Magna and Fourth Ventricle of Cats

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.193.1.207 ◽

1958 ◽

Vol 193 (1) ◽

pp. 207-212 ◽

Cited By ~ 6

Author(s):

John Andrew ◽

Julien Taylor

Keyword(s):

Fourth Ventricle ◽

Cerebral Spinal Fluid ◽

Autonomic Function ◽

Spinal Fluid ◽

Distilled Water ◽

Neural Pathways ◽

Cisterna Magna ◽

The Central Nervous System ◽

Series Of Experiments ◽

The Brain

Following the observation that distilled water, when introduced into the cisterna magna of a cat, produced marked disturbances of autonomic function, a series of experiments was carried out to determine the effect of altering the tonicity of the cerebral spinal fluid. Observations were made on 20 cats under general anesthesia. Precautions were taken to eliminate undesirable effects from raised intracranial pressure. An increase in osmotic tension was found consistently to stimulate respiration and cause marked changes in the electrocardiogram. Reduction of the osmotic tension depressed respiratory function and could cause death. Evidence obtained from a) recording electrical activity in different parts of the brain, b) applying distilled water and hypertonic sodium chloride directly to various parts of the central nervous system, and c) interruption of neural pathways, suggests that an area of special sensitivity to alterations of tonicity in the cerebral spinal fluid exists, and that it is located in the floor of the fourth ventricle.

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Isolated plasmacytoma involving the brain parenchyma and cerebral spinal fluid

Blood ◽

10.1182/blood-2012-12-474072 ◽

2013 ◽

Vol 122 (1) ◽

pp. 6-6 ◽

Cited By ~ 7

Author(s):

Qin Huang

Keyword(s):

Cerebral Spinal Fluid ◽

Brain Parenchyma ◽

Spinal Fluid ◽

The Brain

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Reversible Coma: A Rare Presentation of Spontaneous Intracranial Hypotension

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100003826 ◽

2004 ◽

Vol 31 (4) ◽

pp. 565-568 ◽

Cited By ~ 37

Author(s):

Jodi L. Kashmere ◽

Michael J. Jacka ◽

Derek Emery ◽

Donald W. Gross

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Intracranial Hypotension ◽

Cerebral Spinal Fluid ◽

Spontaneous Intracranial Hypotension ◽

Spinal Fluid ◽

Resonance Imaging ◽

Rare Presentation ◽

Blood Patch ◽

The Brain

Background:Spontaneous intracranial hypotension (SIH) is a well-recognized neurologic disorder that typically presents with orthostatic headaches, low cerebral spinal fluid pressures and distinct abnormalities on magnetic resonance imaging.Methods:We present a case of a rare presentation of SIH.Results:A 49-year-old man presented with a two week history of orthostatic headaches that rapidly progressed to encephalopathy and coma, requiring intubation. Neuroimaging revealed abnormalities typical of SIH; diffusely enhancing pachymeninges, subdural fluid collections, and descent of the brain. Treatment with an epidural blood patch reversed his coma within minutes. Following a second blood patch, the patient became asymptomatic. No cerebral spinal leak could be identified on magnetic resonance imaging or on a nuclear medicine technetium cerebral spinal fluid flow study. At six month follow-up, he remained symptom free.Conclusion:The mechanism of coma in SIH is presumed to be compression of the diencephalon from downward displacement of the brain. Although it is very unusual for patients with SIH to present with coma, it is important to recognize since the coma may be reversible with epidural blood patches.

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