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An insulinoma is a tumour of the pancreas derived from the beta cells which while retaining the ability to synthesize and secrete insulin is autonomous of the normal feedback mechanisms. Patients present with symptomatic hypoglycemia which is ameliorated by feeding. The diagnosis of an insulinoma is usually made biochemically with low blood sugar, elevated insulin, pro-insulin and C-peptide levels and confirmed by medical imaging or angiography. The definitive treatment is surgery. more...

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Insulinomas are rare neuroendocrine tumours with an incidence of 4 in 5 million. They account for 60% of tumours arising from the islets of Langerhans cells. Eighty percent of these tumours are solitary and benign. In 10%, they are malignant (with metastases) and the remainder are multiple tumours. Over 99% of insulinomas are found in the pancreas, with rare cases in ectopic pancreatic tissue. About 5% of cases are associated with tumours of the parathyroid glands and the pituitary (Multiple endocrine neoplasia type 1) and are more likely to be multiple and malignant. Most insulinomas are small, less than 2 cm.

Signs and Symptoms

Patients with insulinomas usually develop neuroglycopenic symptoms. These include recurrent headache, lethargy, diplopia, and blurred vision, particularly with exercise or fasting. Severe hypoglycemia may result in seizures, coma, and permanent neurological damage. Symptoms resulting from the catecholinergic response to hypoglycemia (i.e. tremulousness, palpitations, tachycardia, sweating, hunger, anxiety, nausea) are not as common.


The diagnosis of insulinoma is suspected in a patient with symptomatic fasting hypoglycemia. The conditions of Whipple’s triad need to be met for the diagnosis of hypoglycemia to be made:

1. symptoms and signs of hypoglycemia,
2. concomitant plasma glucose level of 45 mg/dL (2.5 mmol/L) or less, and
3. reversibility of symptoms with administration of glucose.

Blood tests

The following blood tests are needed to diagnose insulinoma:

  • glucose
  • insulin
  • C-peptide

If available, a proinsulin level might be useful as well. Other blood tests may help rule out other conditions which can cause hypoglycemia.

Suppression tests

Normally, endogenous insulin production is suppressed in the setting of hypoglycemia. A 72-hour fast, usually supervised in a hospital setting, can be done to see if insulin levels fail to suppress, which is a strong indicator of the presence of an insulin-secreting tumour.

During the test, the patient may have calorie-free and caffeine-free liquids. Capillary blood glucose is measured every 4 hours using a reflectance meter, until values < 60 mg/dL (3.3 mmol/L) are obtained. Then, the frequency of blood glucose measurement is increased to every hour until values are < 49 mg/dL (2.7 mmol/L). At that point, or when the patient has symptoms of hypoglycemia, a blood test is drawn for serum glucose, insulin, proinsulin, and C-peptide levels. The fast is stopped at that point, and the hypoglycemia treated with intravenous dextrose or calorie-containing food or drink.


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Steady-state and closed-state inactivation properties of inactivating BK channels
From Biophysical Journal, 5/1/02 by Ding, Jiu Ping

ABSTRACT Calcium-dependent potassium (BK-type) Ca^sup 2+^ and voltage-dependent K+ channels in chromaffin cells exhibit an inactivation that probably arises from coassembly of Slo 1 a subunits with auxiliary beta subunits. One goal of this work was to determine whether the Ca^sup 2+^ dependence of inactivation arises from any mechanism other than coupling of inactivation to the Ca^sup 2+^ dependence of activation. Steady-state inactivation and the onset of inactivation were studied in inside-out patches and whole-cell recordings from rat adrenal chromaffin cells with parallel experiments on inactivating BK channels resulting from cloned alpha + beta 2 subunits. In both cases, steady-state inactivation was shifted to more negative potentials by increases in submembrane [Ca^sup 2+^] from 1 to 60 AM. At 10 and 60 (mu) M Ca^sup 2+^, the maximal channel availability at negative potentials was similar despite a shift in the voltage of half availability, suggesting there is no strictly Ca^sup 2+^-dependent inactivation. In contrast, in the absence of Ca^sup 2+^, depolarization to potentials positive to +20 mV induces channel inactivation. Thus, voltagedependent, but not solely Ca-dependent, kinetic steps are required for inactivation to occur. Finally, under some conditions, BK channels are shown to inactivate as readily from closed states as from open states, indicative that a key conformational change required for inactivation precedes channel opening.

We have now proposed two general sorts of physical models that might account for the properties of inactivation we have observed. In one case, inactivation is proposed to result from a conformational change specifically associated with voltage-sensor movement. In the other, a conformational change within the closed channel, allosterically regulated by Ca^sup 2+^ and voltage, is the essential step required for inactivation. Future work will be required to evaluate whether either sort of physical mechanism provides a better account of BK channel inactivation.

This work was supported by DK-46564 and NS-37671 from the National Institutues of Health


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Jiu Ping Ding and Christopher J. Lingle

Washington University School of Medicine, Department of Anesthesiology, St. Louis, Missouri 63110 USA

Submitted November 2, 2001, and accpeted for publication December 12, 2001

Address reprint requests to Chris Lingle, 660 S. Euclid Ave., St. Louis, MO 63110. Tel : 314-362-8558; Fax: 314-362-8571; E-mail: clingle@

Address reprint requests to Chris Lingle, 660 S. Euclid Ave., St. Louis, MO 63110. Tel.: 314-362-8558; Fax: 314-362-8571; E-mail: clingle@

2002 by the Biophysical Society 0006-3495/02/05/2448/18 $2.00

Copyright Biophysical Society May 2002
Provided by ProQuest Information and Learning Company. All rights Reserved

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