Disease relevance of Hyperinsulinism

• The hyperinsulinemia caused secondary insulin resistance with impaired glucose tolerance and random, but not fasting, hyperglycemia [1].
• Hypoglycemia may develop in patients with severe untreated malaria and can complicate the course of treatment with parenteral quinine as a result of quinine-induced hyperinsulinemia [2].
• In six patients with acanthosis nigricans variable degrees of glucose intolerance, hyperinsulinemia and marked resistance to exogenous insulin were found [3].
• Excess risk for cardiovascular disease associated with hyperinsulinemia and glucose intolerance may be mediated in part by enhanced potential for acute thrombosis [4].
• Insulin decreased the levels of potent androgens in PCO women and did not increase androgen levels in normal women, arguing against a simple, direct causal relationship between hyperinsulinemia and hyperandrogenism in PCO [5].

Psychiatry related information on Hyperinsulinism

• Alcohol consumption was significantly and inversely associated with the prevalence of the following three components of the metabolic syndrome: low serum HDL cholesterol, elevated serum triglycerides, high waist circumference, as well as hyperinsulinemia (P <0.05 for all) [6].
• We assessed the effects of induced hyperinsulinemia on plasma and cerebrospinal fluid (CSF) levels of norepinephrine (NE) and on cognition for patients with Alzheimer's disease (AD) and normal older adults [7].
• These findings suggest that a low GI pre-game meal may prolong endurance during strenuous exercise by inducing less post-prandial hyperglycemia and hyperinsulinemia, lower levels of plasma lactate before and during exercise, and by maintaining plasma glucose and FFA at higher levels during critical periods of exercise [8].
• In contrast, unilateral reactivation markedly improved hyperinsulinemia and normalized blood glucose levels and locomotor activity [9].
• Established clinical cutoff points were used to identify 145 participants with mild mental retardation and hyperinsulinemia, borderline high triglycerides, low high-density lipoprotein cholesterol, hypertension, and abdominal obesity [10].

High impact information on Hyperinsulinism

• However, the ability to maintain the degree of compensatory hyperinsulinemia necessary to prevent loss of glucose tolerance in insulin-resistant individuals does not represent an unqualified homeostatic victory [11].
• beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass [12].
• Alström syndrome is a homogeneous autosomal recessive disorder that is characterized by childhood obesity associated with hyperinsulinemia, chronic hyperglycemia and neurosensory deficits [13].
• Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding components of ATP-sensitive K + (KATP) channels), which may be mutated in patients with hyperinsulinism [14].
• We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction [14].

Chemical compound and disease context of Hyperinsulinism

• In addition, the mean (+/- SEM) fasting plasma triglyceride levels in subjects with hyperinsulinemia were significantly higher (1.73 +/- 0.2 vs. 1.24 +/- 0.1 mmol per liter) and the plasma high-density lipoprotein cholesterol concentrations were lower (1.21 +/- 0.06 vs. 1.43 +/- 0.06 mmol per liter) than in subjects with normoinsulinemia [15].
• Seven patients with excessive growth (Group A) had hyperinsulinism, normal IGF values, elevated basal prolactin levels, and a delayed thyrotropin response to thyrotropin-releasing hormone, which was compatible with hypothalamic lesions [16].
• CONCLUSIONS--In NIDDM patients, high-carbohydrate diets compared with high-monounsaturated-fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia, as well as increased plasma triglyceride and very-low-density lipoprotein cholesterol levels, which may not be desirable [17].
• Hyperinsulinemia and uric acid clearance [18].
• On the other hand, the 163-171 fragment did not cause any of several inflammation-associated metabolic changes inducible by the whole IL-1 beta molecule in vivo: hypoferremia, hypoglycemia, hyperinsulinemia, increase in circulating corticosterone, SAA and fibrinogen, decrease in hepatic drug-metabolizing enzymes [19].

Biological context of Hyperinsulinism

• During steady-state euglycemic hyperinsulinemia (about 60 microU per milliliter), hepatic glucose production and lipolysis were effectively suppressed, and glucose oxidation and potassium disposal were normally stimulated [20].
• Familial hyperinsulinism maps to chromosome 11p14-15.1, 30 cM centromeric to the insulin gene [21].
• First, in the presence of physiological hyperinsulinemia (approximately 115 microU/ml), infusion of AII at rates of 2, 10, and 20 ng/min per kg caused significant elevations of blood pressure, whole-body glucose clearance, and plasma insulin concentrations in an AII dose-dependent manner [22].
• Several features of the phenotype, e.g. hyperphagia, tendency toward tall stature, hyperinsulinemia, and preserved reproductive function, closely resemble those reported previously in Mc4r knock-out mice [23].
• Local hyperinsulinemia (deep venous plasma insulin 68.5+/-4 microU/ml) did not change basal FBF whereas attenuated BHT-933 vasoconstriction and enhanced isoproterenol vasodilation [24].

Anatomical context of Hyperinsulinism

• We conclude that healthy persons with hyperinsulinemia and normal glucose tolerance have an increase in risk factors for coronary artery disease, as compared with a well-matched group of healthy subjects with normal insulin levels [15].
• We conclude that 2 wk of continuous hyperinsulinemia results in increased insulin-stimulated glucose metabolism in both adipose cells and soleus muscle [25].
• The mice also exhibited marked decreases in the serum concentrations of FFAs and triglyceride and suppression of insulin-induced PI 3-K activation in adipose tissue, probably due to the associated hyperinsulinemia [26].
• Therefore, chronic experimental hyperinsulinemia in the rat enhances the stimulatory action of insulin on glucose transport in the adipose cell by increasing the concentration of glucose transporters in the plasma membranes [27].
• This reduced clearance is accompanied by compensatory hyperinsulinemia, not hypoinsulinemia, suggesting that the primary defect is in peripheral tissue response to insulin and glucose, not in the pancreatic beta cell [28].

Gene context of Hyperinsulinism

• Ppara+/+, but not Ppara-/-, mice developed hyperglycemia, hyperinsulinemia and hypertension [29].
• Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice [30].
• We have identified the two subunits of the beta-cell ATP-sensitive K(+) channel (K(ATP)), the most frequently mutated genes linked to familial hyperinsulinism, as novel Foxa2 targets in islets [31].
• In mice with too little fat (lipodystrophy) or too much fat (ob/ob), leptin deficiency leads to hyperglycemia, hyperinsulinemia, and insulin resistance [32].
• Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1 [33].

Analytical, diagnostic and therapeutic context of Hyperinsulinism

• Blood flow was measured simultaneously in the bradykinin and insulin- and the insulin-infused leg before and during hyperinsulinemia using [15O]-labeled water ([15O]H2O) and positron emission tomography (PET) [34].
• The present study further suggests that the anomaly of insulin removal observed in perfused livers of ob/ob mice might be secondary to hyperinsulinemia, since it was partly corrected upon artificially decreasing the circulating levels of insulin (e.g. via a fast, anti-insulin serum, or streptozotocin treatment) before perfusion [35].
• We have examined the onset and duration of the inhibitory effect of an intravenous infusion of lipid/heparin on total body carbohydrate and fat oxidation (by indirect calorimetry) and on glucose disappearance (with 6,6 D2-glucose and gas chromatography-mass spectrometry) in healthy men during euglycemic hyperinsulinemia [36].
• Therefore our data show that although hyperglucagonism in rats with partial portal vein ligation and in rats with cirrhosis caused by carbon tetrachloride poisoning is promoted by an enhanced alpha-cell secretion, hyperinsulinism is associated with impaired beta-cell secretion [37].
• Oral glucose-tolerance tests in eight members of her first-degree relatives revealed four members (mother, sister, brother, and daughter) with fasting hyperinsulinemia (111-314 microU/ml), and two of them (mother and sister) were overtly diabetic [38].

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