Incretins today: multiple effects and therapeutic potential

Glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones initially discovered in the 1960s. GIP and GLP-1 have gained great scientific interest due to their properties in increasing insulin secretion and lowering blood glucose levels. The study of these incretin hormones has progressed substantially in recent decades, in that their systemic effects has begun to be actively discussed. In particular, incretins are involved in the pathogenesis of obesity and non-alcoholic fatty liver disease. Moreover, incretins are able to improve cognitive function, suppress the formation of β-amyloid plaques and provide an oncoprotective effect. Recent data show promising oncoprotective effect of GLP-1 agonists on prostate and breast cancer. This review provides systematisation of recent data on the role and mechanisms of action of incretin hormones on carbohydrate metabolism, as well as effects not related to glucose homeostasis, which contributes to a better understanding of potential vectors for the development of incretinotropic therapy. In addition, this review offers insight into pathogenic prerequisites and highlights the current issues in creating innovative polyagonists for treatment of type 2 diabetes mellitus

Long-term uroseptic and metabolic effects of a herbal medicinal preparation in women with type 2 diabetes taken gliflosins

Background. The problem of urinary tract infections, including recurrent cystitis, and the choice of effective and safe means of treatment and prevention, taking into account the increasing burden of antibiotic resistance, are extremely relevant. Aim. To evaluate the effectiveness and safety of the herbal medicine Canephron® N for the prevention of exacerbations of recurrent cystitis and its effect on metabolic parameters in patients with type 2 diabetes mellitus taking sodium glucose cotransporter type 2 inhibitors. Material and methods. A prospective, randomized, open-label, parallel group study of 60 women without exacerbation of recurrent cystitis. The main group took the drug Canephron® N for 3 months, 2 tablets 3 times a day, and for the next 3 months they were monitored without taking the drug. The main evaluation parameters were: frequency of cystitis relapses, albumin/creatinine ratio in the morning urine, glomerular filtration rate, plasma lipid profile, glycemia and malondialdehyde in low-density lipoproteins. Results. 3 months after the end of taking the drug Canephron® N, patients in the main group maintained a positive effect in reducing exacerbations of cystitis – 3.3 times less relapses of the disease (3 and 10%, respectively; p=0.038). The urine albumin/creatinine ratio, lipid profile, glycemia and malondialdehyde in low-density lipoproteins after a 3-month treatment period had positive dynamics, but in the long-term period they corresponded to the values at the inclusion stage, both in the main and control groups. Conclusion. Prophylactic use of the herbal drug Canephron® N for 3 months is safe and reduces the frequency of relapses of cystitis in women with chronic cystitis against the background of diabetes mellitus taking sodium glucose cotransporter type 2 inhibitors, this effect persists for 3 months after discontinuation of the drug. Positive metabolic effects are associated with taking Canephron® N and are gradually leveled out when it is discontinued

Potential new application points of SGLT2 inhibitors in patients with heart failure in combination with diabetes mellitus, non-alcoholic fatty liver disease and anemia (literature review)

Chronic heart failure is a global cardiac problem. The last decade can rightly be called a breakthrough in the treatment of this nosology, due to the emergence of a new group of drugs - SGLT2 inhibitors (gliflozins), which, both in patients with initial heart failure with different ejection fraction, and in the presence of risk factors for its development, have a persistent positive impact on the number of hospitalizations for heart failure. A number of pleiotropic effects of SGLT2 inhibitors are also attractive to the clinician, which include moderate weight loss, a decrease in body fat in visceral fat depots, a decrease in the level of hepatic transaminases in the blood, stimulation of erythropoiesis, which organically complements the strategy of complex cardiorenometabolic protection and emphasizes the unique role of this class drugs in modern cardiology. In the near future, we will have to learn the results of the ongoing multiple studies of gliflozin, which is highly likely to open new historical horizons in the treatment of patients with cardiovascular diseases, including various categories of patients with acute and chronic heart failure

Associations of sex hormones with components of insulin-glucose homeostasis

In this literature review, an attempt is made to analyze the interrelationships of the main sex hormones with the processes of development and progression of insulin resistance as a fundamental pathogenetic component of insulin-glucose homeostasis. In the evaluation of sex steroids, a complex approach was used - the associations of both androgens and estrogens in males and females are described in detail, a great deal of attention is paid to the violation of the secretion and effectiveness of the main adipocytokines - leptin and adiponectin in the sex hormone-insulin-glucose interaction chain. At the end of the review, new data on the expression of sodium-dependent glucose cotransporter (SGLT) and glucose transporters (GLUT) in animals, depending on sex, are presented

Preliminary paleoenvironmental analysis of permafrost deposits at Batagaika megaslump, Yana Uplands, northeast Siberia

A megaslump at Batagaika, in northern Yakutia, exposes a remarkable stratigraphic sequence of permafrost deposits ~50–80 m thick. To determine their potential for answering key questions about Quaternary environmental and climatic change in northeast Siberia, we carried out a reconnaissance study of their cryostratigraphy and paleoecology, supported by four rangefinder 14C ages. The sequence includes two ice complexes separated by a unit of fine sand containing narrow syngenetic ice wedges and multiple paleosols. Overall, the sequence developed as permafrost grew syngenetically through an eolian sand sheet aggrading on a hillslope. Wood remains occur in two forest beds, each associated with a reddened weathering horizon. The lower bed contains high amounts of Larix pollen (>20%), plus small amounts of Picea and Pinus pumila, and is attributed to interglacial conditions. Pollen from the overlying sequence is dominated by herbaceous taxa (~70%–80%) attributed to an open tundra landscape during interstadial climatic conditions. Of three hypothetical age schemes considered, we tentatively attribute much of the Batagaika sequence to Marine Oxygen Isotope Stage (MIS) 3. The upper and lower forest beds may represent a mid–MIS 3 optimum and MIS 5, respectively, although we cannot discount alternative attributions to MIS 5 and 7