Metabolism Research Center

San Donato di Ninea, Italy

Metabolism Research Center

San Donato di Ninea, Italy

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Benedini S.,University of Milan | Benedini S.,Endocrinology Unit | Dozio E.,University of Milan | Invernizzi P.L.,University of Milan | And 9 more authors.
Journal of Diabetes Research | Year: 2017

We compared irisin levels among groups of differently trained healthy individuals to explore the role of irisin as a physiological linker between exercise and metabolic health. Irisin and biochemical parameters of glucose and lipid metabolism were assessed in 70 healthy volunteers stratified for sport performance level into four groups: (1) 20 elite athletes of national level, (2) 20 subelite athletes of local level, (3) 20 recreational athletes, and (4) 10 sedentary subjects. All biochemical parameters were within the ranges of normality. Fasting glucose, HOMA-IR, and total cholesterol levels were inversely related to the degree of physical activity. HbA1c was higher in elite athletes compared to all the other groups (p<0.01). A U-shaped relation between free fatty acids and the degree of physical activity was observed. All groups showed similar plasma irisin levels. After correction for the degree of insulin resistance (irisin/HOMA-IR), elite athletes showed higher levels compared to sedentary and recreational subjects (p<0.01 and p<0.05, resp.). In addition, the number of metabolic parameters correlated with irisin increased at increasing the training status. Our study suggests a correlation between sport performance, insulin sensitivity, and irisin levels. Irisin may be one potential mediator of the beneficial effects of exercise on metabolic profile. Copyright © 2017 Stefano Benedini et al.


Adamo M.,University of Milan | Adamo M.,Metabolism Research Center | Codella R.,University of Milan | Codella R.,Metabolism Research Center | And 11 more authors.
Cell Transplantation | Year: 2017

Previous studies in humans with type 1 diabetes mellitus (T1D) and in nonobese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity. Performing high volume of aerobic exercise may favorably regulate autoimmunity in diabetes. We tested whether increased physical activity is a self-sufficient positive factor in T1D subjects. During a 3-month observational period, active (six males; 40.5 ± 6.1 years; BMI: 24.5 ± 2.1) and sedentary (four males, three females; 35.9 ± 8.9 years; BMI: 25.7 ± 3.8) T1D individuals on insulin pump therapy were studied for metabolic, inflammatory, and autoimmune parameters. At baseline and at the end of a 3-month period, glycosylated hemoglobin (HbA1c), autoantibodies (anti-GAD, anti-ZnT8, anti-IA2, and ICA) and proinflammatory cytokines (IL-6 and TNF-a) were evaluated. During the third month of the period, physically active T1D patients showed a significant reduction in the average glucose levels (−9%, p = 0.025, by CGM) compared to the first month values, and even their hyperglycemic episodes (>180 mg/dl) diminished significantly (−24.2%, p = 0.032 vs. first month). Moreover, active T1D subjects exhibited an improved body composition with respect to sedentary controls. No significant changes were detected as to the autoimmune and inflammatory profiles. This study confirms the beneficial role of physical exercise associated with insulin pump therapy in order to improve metabolic control in individuals with T1D. These preliminary positive observations need to be challenged in a prolonged interventional follow-up. © 2017 Cognizant, LLC.


Codella R.,University of Milan | Terruzzi I.,San Raffaele Scientific Institute | Luzi L.,University of Milan | Luzi L.,Metabolism Research Center
Acta Diabetologica | Year: 2017

Abstract: Plethoric evidence reminds of the protective effects of exercise against a number of health risks, across all ages, in the general population. The benefits of exercise for individuals with type 2 diabetes are indisputable. An in-depth understanding of energy metabolism has reasonably entailed exercise as a cornerstone in the lifestyle of almost all subjects with type 1 diabetes. Nevertheless, individuals with type 1 diabetes often fail in accomplishing exercise guidelines and they are less active than their peer without diabetes. Two major obstacles are feared by people with type 1 diabetes who wish to exercise regularly: management of blood glucose control and hypoglycemia. Nowadays, strategies, including glucose monitoring technology and insulin pump therapy, have significantly contributed to the participation in regular physical activity, and even in competitive sports, for people with type 1 diabetes. Novel modalities of training, like different intensity, interspersed exercise, are as well promising. The beneficial potential of exercise in type 1 diabetes is multi-faceted, and it has to be fully exploited because it goes beyond the insulin-mimetic action, possibly through immunomodulation. © 2017 Springer-Verlag Italia


Codella R.,University of Milan | Codella R.,University of Miami | Codella R.,Metabolism Research Center | Lanzoni G.,University of Miami | And 10 more authors.
Journal of Diabetes Research | Year: 2015

The nonobese diabetic (NOD) mouse represents a well-established experimental model analogous to human type 1 diabetes mellitus (T1D) as it is characterized by progressive autoimmune destruction of pancreatic β-cells. Experiments were designed to investigate the impact of moderate-intensity training on T1D immunomodulation and inflammation. Under a chronic exercise regime, NOD mice were trained on a treadmill for 12 weeks (12 m/min for 30 min, 5 d/wk) while age-matched, control animals were left untrained. Prior to and upon completion of the training period, fed plasma glucose and immunological soluble factors were monitored. Both groups showed deteriorated glycemic profiles throughout the study although trained mice tended to be more compensated than controls after 10 weeks of training. An exercise-induced weight loss was detected in the trained mice with respect to the controls from week 6. After 12 weeks, IL-6 and MIP-1β were decreased in the trained animals compared to their baseline values and versus controls, although not significantly. Morphometric analysis of pancreata revealed the presence of larger infiltrates along with decreased α-cells areas in the control mice compared to trained mice. Exercise may exert positive immunomodulation of systemic functions with respect to both T1D and inflammation, but only in a stringent therapeutic window. © 2015 Roberto Codella et al.


PubMed | San Raffaele Scientific Institute, Metabolism Research Center and University of Milan
Type: | Journal: Endocrine | Year: 2016

The purpose of this study is to investigate Ranolazine action on skeletal muscle differentiation and mitochondrial oxidative phenomena. Ranolazine, an antianginal drug, which acts blocking the late INaL current, was shown to lower hemoglobin A1c in patients with diabetes. In the present study, we hypothesized an action of Ranolazine on skeletal muscle cells regeneration and oxidative process, leading to a reduction of insulin resistance.10M Ranolazine was added to C2C12 murine myoblastic cells during proliferation, differentiation and newly formed myotubes.Ranolazine promoted the development of a specific myogenic phenotype: increasing the expression of myogenic regulator factors and inhibiting cell cycle progression factor (p21). Ranolazine stimulated calcium signaling (calmodulin-dependent kinases) and reduced reactive oxygen species levels. Furthermore, Ranolazine maintained mitochondrial homeostasis. During the differentiation phase, Ranolazine promoted myotubes formation. Ranolazine did not modify kinases involved in skeletal muscle differentiation and glucose uptake (extracellular signal-regulated kinases 1/2 and AKT pathways), but activated calcium signaling pathways. During proliferation, Ranolazine did not modify the number of mitochondria while decreasing osteopontin protein levels. Lastly, neo-formed myotubes treated with Ranolazine showed typical hypertrophic phenotype.In conclusion, our results indicate that Ranolazine stimulates myogenesis and reduces a pro-oxidant inflammation/oxidative condition, activating a calcium signaling pathway. These newly described mechanisms may partially explain the glucose lowering effect of the drug.


PubMed | San Raffaele Scientific Institute, Metabolism Research Center, University of Miami and University of Milan
Type: | Journal: Cell transplantation | Year: 2016

Previous studies in humans with type 1 diabetes (T1D) and in non-obese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity. Performing high volume of aerobic exercise may favorably regulate autoimmunity in diabetes. We tested whether increased physical activity is a self-sufficient positive factor in T1D subjects.

During a 3-month observational period, active (6M; 40.56.1 years; BMI 24.52.1) and sedentary (4M, 3F; 35.98.9 years; BMI 25.73.8) T1D individuals on insulin pump therapy were studied for metabolic, inflammatory and autoimmune parameters. At baseline and at the end of a 3-month period, glycosylated hemoglobin (HbA1c), auto-antibodies (anti-GAD, anti-ZnT8, anti-IA2, ICA) and pro-inflammatory cytokines (IL-6 and TNF-) were evaluated. During the 3rd month of the period, physically active T1D patients showed a significant reduction in the average glucose levels (-9%, p=0.025, by CGM) compared to the 1st-month values, and even their hyperglycemic episodes (>180mg/dL) diminished significantly (-24.2%, p=0.032 vs 1st month). Moreover, active T1D subjects exhibited an improved body composition with respect to sedentary controls. No significant changes were detected as to the autoimmune and inflammatory profiles.

This study confirms the beneficial role of physical exercise associated with insulin pump therapy in order to improve metabolic control in individuals with T1D. These preliminary positive observations need to be challenged in a prolonged interventional follow-up.


PubMed | Metabolism Research Center, Endocrinology Unit and University of Milan
Type: | Journal: Case reports in endocrinology | Year: 2015

Type 1 diabetes mellitus (T1D), autoimmune thyroid disease, and autoimmune gastritis often occur together forming the so-called autoimmune polyendocrine syndrome type 3 (APS3). We here report a clinical case of a 74-year-old woman who presented for the first time with severe hyperglycemia and ketoacidosis diagnosed as T1D. Further clinical investigations revealed concomitant severe hypothyroidism with autoimmune thyroid disease and severe cobalamin deficiency due to chronic atrophic gastritis. The diagnosis of type 1 diabetes mellitus was confirmed by the detection of autoantibodies against glutamic acid decarboxylase 65, islet cell antibodies, and anti-insulin autoantibodies. Anti-thyroperoxidase, anti-thyroglobulin, and anti-gastric parietal cell antibodies were also clearly positive. The case emphasized that new onset diabetic ketoacidosis, hypothyroidism, and cobalamin deficiency may simultaneously occur, and one disease can mask the features of the other, thereby making diagnosis difficult. It is noteworthy that an APS3 acute episode occurred in an asymptomatic elder woman for any autoimmune diseases.


Formenti D.,University of Milan | Ludwig N.,University of Milan | Trecroci A.,University of Milan | Gargano M.,University of Milan | And 4 more authors.
Journal of Thermal Biology | Year: 2016

Low intensity resistance training with slow movement and tonic force generation has been shown to create blood flow restriction within muscles that may affect thermoregulation through the skin. We aimed to investigate the influence of two speeds of exercise execution on skin temperature dynamics using infrared thermography. Thirteen active males performed randomly two sessions of squat exercise (normal speed, 1 s eccentric/1 s concentric phase, 1 s; slow speed, 5 s eccentric/5 s concentric phase, 5 s), using ~50% of 1 maximal repetition. Thermal images of ST above muscles quadriceps were recorded at a rate of 0.05 Hz before the exercise (to determine basal ST) and for 480 s following the initiation of the exercise (to determine the nonsteady-state time course of ST). Results showed that ST changed more slowly during the 5 s exercise (p=0.002), whereas the delta (with respect to basal) excursions were similar for the two exercises (p>0.05). In summary, our data provided a detailed nonsteady-state portrait of ST changes following squat exercises executed at two different speeds. These results lay the basis for further investigations entailing the joint use of infrared thermography and Doppler flowmetry to study the events taking place both at the skin and the muscle level during exercises executed at slow speed. © 2016 Elsevier Ltd.

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