Little is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2a4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2a4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2.5 to 7.5 hours. In vivo, AGE-albumin induced whole-body insulin resistance; decreased (~30%) Slc2a4 mRNA and GLUT4 protein content; and increased (~30%) the nuclear content of nuclear factor NF-kappa-B p50 subunit (NFKB1), and cellular content of 78 kDa glucose-regulated protein (GRP78). In vitro, incubation with AGE-albumin decreased (~50%) the Slc2a4/GLUT4 content; and increased cellular content of GRP78/94, phosphorylated-IKK-alpha/beta, nuclear content of NFKB1 and RELA, and the nuclear protein binding into Slc2a4 promoter NFKB-binding site. The data reveal that AGEs impair glucose homeostasis in non-diabetic states of increased AGEs concentration; an effect that involves activation of endoplasmic reticulum- and inflammatory-stress and repression of Slc2a4/GLUT4 expression.

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population.

Lima GA, Anhê GF, Giannocco G, Nunes MT, Correa-Giannella ML, Machado UF. Contractile activity per se induces transcriptional activation of SLC2A4 gene in soleus muscle: involvement of MEF2D, HIF-1a, and TR␣ transcriptional factors.

Aims To evaluate diabetic retinopathy (DR) screening with a portable handheld smartphone-based retinal camera and telemedicine in an urban primary healthcare setting and to evaluate the learning curve for image acquisition, performed by healthcare personnel without previous experience in retinal imaging. Methods This was a prospective study that enrolled patients with type 2 diabetes mellitus (T2DM) followed at a primary healthcare unit in São Paulo, Brazil. After a brief training in image acquisition, there was further continuous feedback given by a retina specialist during the remote image reading process. Each patient underwent two fundus and one anterior ocular segment images per eye, after mydriasis. Patients were classified according to the need of referral. Results A total of 627 adult individuals with T2DM underwent retinal evaluation. The population was composed by 63.2% female individuals, age median of 66 years, diabetes duration 10.7 ± 8.2 years and HbA1c 7.7 ± 1.9% (61 + 20.8 mmol/mol). The most prevalent associated comorbidities were arterial hypertension (80.3%) and dyslipidemia (50.2%). Referral decision was possible in 81.2% patients. Most patients had absent or non-referable DR; the main ocular media opacity detected was cataract. After the 7th day of image acquisition, the daily rate of patients whose images allowed clinical decision was maintained above 80%. A higher HbA1c was associated with referable DR. Conclusions A low-cost DR screening strategy with a handheld device and telemedicine is feasible and has the potential to increase coverage of DR screening in underserved areas; the possibility of mobile units is relevant for DR screening in the context of COVID-19 pandemic. This article belongs to the topical collection Eye Complications of Diabetes, managed by Giuseppe Querques.