Paolina Milazzo

Animal and human tissue Na,K-ATPase in obesity and diabetes: A new proposed enzyme regulation.

Background:Na,K-ATPase is a membrane enzyme that energizes the Na-pump, hydrolyzing ATP and wasting energy as heat. It may play a role in thermogenesis, energy balance, and obesity development. Regulation of the enzyme by insulin is controversial. Methods:In animal and human obesity, tissue Na,K-ATPase was assayed by colorimetric measurement of released Pi. Results:Na,K-ATPase of hyperglycemic-hyperinsulinemic ob/ob mice (compared with lean control animals) was reduced in liver (−63%) and in kidney (−47%) (P < 0.001 in both instances). In contrast, in streptozotocin-treated hypoinsulinemic-diabetic Swiss mice, versus untreated animals, we found an increase of liver (+54%, P < 0.01) and kidney (+94%, P < 0.001) Na,K-ATPase. The enzyme was also increased (+99%, P < 0.05) in kidney from ob/ob mice made diabetic-hypoinsulinemic with streptozotocin (versus untreated obese animals). This is contrary to the occurrence of a genetic enzymatic defect and suggests regulation by hyperinsulinemia, present in ob/ob mice. A positive correlation between tissue enzyme activity and glycemia existed in both ob/ob and Swiss mice. In adipose tissue from obese patients (compared with lean subjects), Na,K-ATPase was reduced (−65%, P < 0.001) and negatively correlated with body mass index, oral glucose tolerance test—insulinemic area, and mean blood pressure. In vitro, in human liver tissue, 3 &mgr;g/mL glucagon exerted a statistically inhibitory effect on Na,K-ATPase (−44%). Conclusion:We hypothesize that animal and human obesity is associated with reduction of tissue Na,K-ATPase, linked to hyperinsulinemia, which may repress or inactivate the enzyme, influencing thermogenesis and energy balance.

Rheumatoid Syndrome Associated with Lung Interstitial Disorder in a Dental Technician Exposed to Ceramic Silica Dust. A Case Report and Critical Literature Review

Abstract Exposure to silica minerals is associated with silicosis and autoimmune disorders, especially systemic scleroderma. Evidence of this association has been increasingly reported in the last decade. The aim of this paper is to discuss, on the basis of a literature review, the case of a 28-year-old female dental technician who suffered from episodes of weakness, arthralgia, pain, swelling and stiffness of the fingers, dyspnoea with cough, a positive Waaler–Rose reaction, increased rheumatoid factor and normal ESR. She was a non-smoker. A rheumatoid syndrome with lung interstitial disorder, associated with silica exposure from dental ceramic products, was diagnosed. The patient had the HLA-A2-A31, HLA-B51-B18 and HLA-DR3-DR11 haplotypes, some of which are associated with autoimmune disease susceptibility. A 6-month follow-up, with adequate protection and without treatment, showed disappearance of the symptomatology and negative tests for Waaler–Rose reaction and rheumatoid factor. Exposure to silica should, therefore, be sought in the history of any patient with autoimmune or lupus-like syndrome and pulmonary changes. Symptoms associated with silica dust exposure from dental ceramic products should be recognised as being due potentially to an occupational disease, and dental technicians should be protected as workers at risk.

Animal and human tissue Na,K-ATPase in normal and insulin-resistant states: regulation, behaviour and interpretative hypothesis on NEFA effects.

The sodium(Na)‐ and potassium(K)‐activated adenosine‐triphosphatase (Na,K‐ATPase) is a membrane enzyme that energizes the Na‐pump by hydrolysing adenosine triphosphate and wasting energy as heat, so playing a role in thermogenesis and energy balance. Na,K‐ATPase regulation by insulin is controversial; in tissue of hyperglycemic‐hyperinsulinemic ob/ob mice, we reported a reduction, whereas in streptozotocin‐treated hypoinsulinemic‐diabetic Swiss and ob/ob mice we found an increased activity, which is against a genetic defect and suggests a regulation by hyperinsulinemia. In human adipose tissue from obese patients, Na,K‐ATPase activity was reduced and negatively correlated with body mass index, oral glucose tolerance test‐insulinemic area and blood pressure. We hypothesized that obesity is associated with tissue Na,K‐ATPase reduction, apparently linked to hyperinsulinemia, which may repress or inactivate the enzyme, thus opposing thyroid hormones and influencing thermogenesis and obesity development. Insulin action on Na,K‐ATPase, in vivo, might be mediated by the high level of non‐esterified fatty acids, which are circulating enzyme inhibitors and increase in obesity, diabetes and hypertension. In this paper, we analyse animal and human tissue Na,K‐ATPase, its level, and its regulation and behaviour in some hyperinsulinemic and insulin‐resistant states; moreover, we discuss the link of the enzyme with non‐esterified fatty acids and attempt to interpret and organize in a coherent view the whole body of the exhaustive literature on this complicated topic.

Effects of short-term metformin treatment on insulin sensitivity of blood glucose and free fatty acids

Aim:u2002 Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short‐term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD). We used a method to allow us to evaluate the possible difference of insulin sensibility with regard to the insulin action on glycaemia and blood FFA, both in the basal state and during oral glucose tolerance test (OGTT).

A Mild Form of Alstrom Disease Associated with Metabolic Syndrome and Very High Fasting Serum Free Fatty Acids: Two Cases Diagnosed in Adult Age

&NA; Alstrom syndrome (ALMS) is a very rare genetic autosomal recessive disease, characterized by early‐onset severe abdominal obesity, impaired glucose tolerance or type 2 diabetes with insulin resistance, acanthosis nigricans, hyperlipidemia, childhood progressive retinal degeneration or retinitis pigmentosa and neurosensory hearing loss or deafness, cardiomyopathy, and other endocrine disorders. Genetic studies locate the ALMS gene on chromosome 2p12–13. The aim of this paper is to describe and discuss two unrelated cases of a mild ALMS form diagnosed after the age of 40 and 60, respectively, in adult fertile female patients. These cases showed several features of the disease plus other alterations characteristic of the classic “metabolic syndrome,” including hypertension, hyperfibrinogenemia, and thrombotic states. Moreover, the patients had very high fasting serum free fatty acid (FFA) levels (2150 and 1919 &mgr;mol/L, respectively), which proved to be sensitive to inhibition by oral glucose tolerance test (OGTT)–induced hyperinsulinemia as well as to caloric restriction. ALMS may have an adverse prognosis and is often underdiagnosed. Its mild form, which allows a long survival, may also be associated with the late complications of the metabolic syndrome, leading to increased vascular risk.