Fabrizia Bonacina1, Andrea Baragetti1,2, Alberico Luigi Catapano1,3, Giuseppe Danilo Norata4,5. 1. Department of Excellence of Pharmacological and Biomolecular Sciences (DisFeB), Università Degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. 2. SISA Centre, Bassini Hospital, 20092, Cinisello Balsamo, Italy. 3. IRCSS Multimedica, 20138, Milan, Italy. 4. Department of Excellence of Pharmacological and Biomolecular Sciences (DisFeB), Università Degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy. danilo.norata@unimi.it. 5. SISA Centre, Bassini Hospital, 20092, Cinisello Balsamo, Italy. danilo.norata@unimi.it.
Abstract
PURPOSE OF REVIEW: Metabolic reprogramming is increasingly recognized as an essential trait of functional activation of immune cells. Here, we describe the link between immuno-metabolism, diabetes, and diabetic nephropathy. RECENT FINDINGS: Crosstalk between cellular metabolic functions and immune activation occurs when plasma levels of glucose, triglycerides, and free fatty acids increase, thus promoting systemic low-grade inflammation that further boosts the development of metabolic complications. In the long run, this settles an "apparent paradox," where, despite excessive inflammation, the immune system is suppressed, further promoting progression to end-stage renal disease (ESRD) and predisposing to premature deaths from infections and cardiovascular diseases. Reviewing the effects of diabetes treatments on immuno-inflammatory responses suggests that the benefit of these drugs might extend beyond the simple control of glucose homeostasis. Hyperglycemia and dyslipidemia correlate with enhancement of the immuno-inflammatory response that can promote and worsen metabolic diseases and support the progression toward ESRD. The identification of cellular checkpoints that modulate the immuno-metabolic machinery of immune cells opens new venues for metabolic drugs.
PURPOSE OF REVIEW: Metabolic reprogramming is increasingly recognized as an essential trait of functional activation of immune cells. Here, we describe the link between immuno-metabolism, diabetes, and diabetic nephropathy. RECENT FINDINGS: Crosstalk between cellular metabolic functions and immune activation occurs when plasma levels of glucose, triglycerides, and free fatty acids increase, thus promoting systemic low-grade inflammation that further boosts the development of metabolic complications. In the long run, this settles an "apparent paradox," where, despite excessive inflammation, the immune system is suppressed, further promoting progression to end-stage renal disease (ESRD) and predisposing to premature deaths from infections and cardiovascular diseases. Reviewing the effects of diabetes treatments on immuno-inflammatory responses suggests that the benefit of these drugs might extend beyond the simple control of glucose homeostasis. Hyperglycemia and dyslipidemia correlate with enhancement of the immuno-inflammatory response that can promote and worsen metabolic diseases and support the progression toward ESRD. The identification of cellular checkpoints that modulate the immuno-metabolic machinery of immune cells opens new venues for metabolic drugs.
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