scholarly journals Proglucagon-Derived Peptides as Therapeutics

2021 ◽  
Vol 12 ◽  
Author(s):  
Ryan A. Lafferty ◽  
Finbarr P. M. O’Harte ◽  
Nigel Irwin ◽  
Victor A. Gault ◽  
Peter R. Flatt
Keyword(s):  
Bone Health ◽  
Clinical Development ◽  
Prohormone Convertase ◽  
Energy Regulation ◽  
Physiological Effects ◽  
Appetite Control ◽  
Successful Design ◽  
Long Acting ◽  
Pancreatic Peptide

Initially discovered as an impurity in insulin preparations, our understanding of the hyperglycaemic hormone glucagon has evolved markedly over subsequent decades. With description of the precursor proglucagon, we now appreciate that glucagon was just the first proglucagon-derived peptide (PGDP) to be characterised. Other bioactive members of the PGDP family include glucagon-like peptides -1 and -2 (GLP-1 and GLP-2), oxyntomodulin (OXM), glicentin and glicentin-related pancreatic peptide (GRPP), with these being produced via tissue-specific processing of proglucagon by the prohormone convertase (PC) enzymes, PC1/3 and PC2. PGDP peptides exert unique physiological effects that influence metabolism and energy regulation, which has witnessed several of them exploited in the form of long-acting, enzymatically resistant analogues for treatment of various pathologies. As such, intramuscular glucagon is well established in rescue of hypoglycaemia, while GLP-2 analogues are indicated in the management of short bowel syndrome. Furthermore, since approval of the first GLP-1 mimetic for the management of Type 2 diabetes mellitus (T2DM) in 2005, GLP-1 therapeutics have become a mainstay of T2DM management due to multifaceted and sustainable improvements in glycaemia, appetite control and weight loss. More recently, longer-acting PGDP therapeutics have been developed, while newfound benefits on cardioprotection, bone health, renal and liver function and cognition have been uncovered. In the present article, we discuss the physiology of PGDP peptides and their therapeutic applications, with a focus on successful design of analogues including dual and triple PGDP receptor agonists currently in clinical development.

Experience in clinical practice with new long-acting insulins in type 2 diabetes (T2D)

2018 ◽  
Author(s):  
Maria Molina Vega ◽  
Araceli Munoz Garach ◽  
Miguel Damas Fuentes ◽  
Carmen Hernandez Garcia ◽  
Cristina Diaz Perdigones ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Practice ◽  
Long Acting

scholarly journals Mood and Metabolic Health Status of Elderly Osteoporotic Patients in Korea: A Cross-Sectional Study of a Nationally Representative Sample

Healthcare ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 77
Author(s):  
Hyen Chul Jo ◽  
Gu-Hee Jung ◽  
Seong-Ho Ok ◽  
Ji Eun Park ◽  
Jong Chul Baek
Keyword(s):  
Abdominal Obesity ◽  
Bone Health ◽  
Elderly Women ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Standard Procedures ◽  
Nationally Representative ◽  
Male Subjects ◽  
Female Subjects

This study aimed to investigate the association between osteoporosis and comorbidity, which are very common in Korea, and develop a treatment strategy to improve bone health based on the findings of the Korean National Health and Nutritional Examination Surveys (KNHANES). This study was based on data obtained from 4060 subjects (1755 males, 2305 females) aged above 60 years in the KNHANES (2016–2017). Well-trained medical staff performed the standard procedures and measured several variables including height, weight, and waist circumference. Interviews and laboratory tests were based on the diagnosis of hyperuricemia, dyslipidemia, type 2 diabetes mellitus (T2DM), osteoporosis, and depression. Comorbidities were defined as a self-reported physician diagnosis. The association of osteoporosis with depression and metabolic disease was assessed statistically using the complex sample analysis method of SPSS. The presence of osteoporosis, dyslipidemia, T2DM, hyperuricemia, obesity, abdominal obesity, and depression was 6.1 ± 0.5%, 15.2 ± 0.7%, 6.5 ± 0.4%, 13.4 ± 0.7%, 30.8 ± 0.8%, 19.4 ± 0.9%, 4.0 ± 0.2%, respectively. After adjusted by age, osteoporotic subjects were significance in the presence of abdominal obesity (p = 0.024, OR 0.80), hyperuricemia (p = 0.013, OR 0.68), dyslipidemia (p < 0.001, OR 1.84), and depression (p < 0.001, OR 2.56), respectively. Subgroup analyses showed dyslipidemia (female subjects, p < 0.001, OR 1.04; male subjects, p = 0.94, OR 1.09) and depression (female subjects, p < 0.001, OR 1.76; male subjects, p = 0.51, OR 0.62) were associated with osteoporotic female subjects but not in male subjects. The comorbidity of dyslipidemia and depression in female subjects was associated with osteoporosis and an odds ratio was 13.33 (95% CI: 8.58–20.71) (p < 0.001). The comorbidity of abdominal obesity (female subjects, p = 0.75, OR 0.97; male subjects, p = 0.94, OR 1.02) and hyperuricemia (female subjects, p = 0.27, OR 0.81; male subjects p = 0.07, OR 0.35) was not associated with osteoporosis in both Subgroup. The result of this study shows a strong dependency of comorbidity with dyslipidemia and depression in elderly women with osteoporosis. Therefore, efforts to improve dyslipidemia and depression might prevent compromised bone health.

scholarly journals The Potential Nutrition-, Physical- and Health-Related Benefits of Cow’s Milk for Primary-School Aged Children

2021 ◽  
pp. 1-42
Author(s):  
Penny Rumbold ◽  
Nicola McCullogh ◽  
Ruth Boldon ◽  
Crystal Haskell-Ramsay ◽  
Lewis James ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Primary School ◽  
Bone Health ◽  
Cow’S Milk ◽  
Milk Consumption ◽  
Appetite Control ◽  
Cow's Milk ◽  
School Aged Children ◽  
Health Related ◽  
Physical Stature

Abstract Cow’s milk is a naturally nutrient-dense foodstuff. A significant source of many essential nutrients, its inclusion as a component of a healthy balanced diet has been long recommended. Beyond milk’s nutritional value, an increasing body of evidence illustrates cow’s milk may confer numerous benefits related to health. Evidence from adult populations suggests that cow’s milk may have a role in overall dietary quality, appetite control, hydration and cognitive function. Although evidence is limited compared to the adult literature, these benefits may be echoed in recent paediatric studies. This article, therefore, reviews the scientific literature to provide an evidence-based evaluation of the associated health benefits of cow’s milk consumption in primary-school aged children (4-11 years). We focus on seven key areas related to nutrition and health comprising nutritional status, hydration, dental and bone health, physical stature, cognitive function, and appetite control. The evidence consistently demonstrates cow’s milk (plain and flavoured) improves nutritional status in primary-school aged children. With some confidence, cow’s milk also appears beneficial for hydration, dental and bone health and beneficial to neutral concerning physical stature and appetite. Due to conflicting studies, reaching a conclusion has proven difficult concerning cow’s milk and cognitive function therefore a level of caution should be exercised when interpreting these results. All areas, however, would benefit from further robust investigation, especially in free-living school settings, to verify conclusions. Nonetheless, when the nutritional-, physical- and health-related impact of cow’s milk avoidance is considered, the evidence highlights the importance of increasing cow’s milk consumption.

scholarly journals Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2

2006 ◽  
Vol 13 (3) ◽  
pp. 955-962 ◽  
Author(s):  
E Ferrante ◽  
C Pellegrini ◽  
S Bondioni ◽  
E Peverelli ◽  
M Locatelli ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cultured Cells ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Somatostatin Analogs ◽  
Receptor Type ◽  
Apoptotic Activity ◽  
Long Acting ◽  
Induced Apoptosis

Somatostatin analogs currently used in the treatment of acromegaly and other neuroendocrine tumors inhibit hormone secretion and cell proliferation by binding to somatostatin receptor type (SST) 2 and 5. The antiproliferative pathways coupled to these receptors have been only partially characterized. The aim of this study was to evaluate the effect of octreotide and super selective SST2 (BIM23120) and SST5 (BIM23206) analogs on apoptotic activity and apoptotic gene expression in human somatotroph tumor cells. Eight somatotroph tumors expressing similar levels of SST2 and SST5 evaluated by real-time PCR and western blot analyses were included in the study. In cultured cells obtained from these tumors, octreotide induced a dose-dependent increase of caspase-3 activity (160 ± 20% vs basal at 10 nM) and cleaved cytokeratin 18 levels (172 ± 25% vs basal) at concentrations higher than 0.1 nM. This effect was due to SST2 activation since BIM23120 elicited comparable responses, while BIM23206 was ineffective. BIM23120-stimulated apoptosis was dependent on phosphatases, since it was abrogated by the inhibitor orthovanadate, and independent from the induction of apoptosis-related genes, such as p53, p63, p73, Bcl-2, Bax, BID, BIK, TNFSF8, and FADD. In somatotroph tumors, both BIM23120 and BIM2306 caused growth arrest as indicated by the increase in p27 and decrease in cyclin D1 expression. In conclusion, the present study showed that octreotide-induced apoptosis in human somatotroph tumor cells by activating SST2. This effect, together with the cytostatic action exerted by both SST2 and SST5 analogs, might account for the tumor shrinkage observed in acromegalic patients treated with long-acting somatostatin analogs.

scholarly journals Pasireotide in an insulin-requiring diabetic acromegalic patient without worsening of hyperglycemia

2017 ◽  
Vol 2017 ◽  
Author(s):  
Murray B Gordon ◽  
Kellie L Spiller
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
List Type ◽  
Effective Treatment Option ◽  
Patients With Diabetes ◽  
Long Acting ◽  
Learning Points

Summary Long-acting pasireotide is an effective treatment option for acromegaly, but it is associated with hyperglycemia, which could impact its use in patients with diabetes. We present a case of a 53-year-old man with acromegaly and type 2 diabetes mellitus (glycated hemoglobin (HbA1c): 7.5%), who refused surgery to remove a pituitary macroadenoma and enrolled in a Phase 3 clinical trial comparing long-acting pasireotide and long-acting octreotide in acromegalic patients. The patient initially received octreotide, but insulin-like growth factor 1 (IGF-1) levels remained elevated after 12 months (383.9 ng/mL; 193.0 ng/mL; reference range: 86.5–223.8 ng/mL), indicating uncontrolled acromegaly. He switched to pasireotide 40 mg and subsequently increased to 60 mg. Within 6 months, IGF-1 levels normalized (193.0 ng/mL), and they were mostly normal for the next 62 months of treatment with pasireotide (median IGF-1: 190.7 ng/mL). Additionally, HbA1c levels remained similar to or lower than baseline levels (range, 6.7% to 7.8%) during treatment with pasireotide despite major changes to the patient’s antidiabetic regimen, which included insulin and metformin. Uncontrolled acromegaly can result in hyperglycemia due to an increase in insulin resistance. Despite having insulin-requiring type 2 diabetes, the patient presented here did not experience a long-term increase in HbA1c levels upon initiating pasireotide, likely because long-term control of acromegaly resulted in increased insulin sensitivity. This case highlights the utility of long-acting pasireotide to treat acromegaly in patients whose levels were uncontrolled after long-acting octreotide and who manage diabetes with insulin. Learning points Long-acting pasireotide provided adequate, long-term biochemical control of acromegaly in a patient with insulin-requiring type 2 diabetes mellitus who was unresponsive to long-acting octreotide. Glycemic levels initially increased after starting treatment with pasireotide but quickly stabilized as acromegaly became controlled. Long-acting pasireotide, along with an appropriate antidiabetic regimen, may be a suitable therapy for patients with acromegaly who also have insulin-requiring type 2 diabetes mellitus.

scholarly journals The experience with the clinical application of liralgutide (victosa), the first analog of human glucagon-like peptide-1 in the patients with type 2 diabetes mellitus - expanding the range of possibilities

2012 ◽  
Vol 58 (3) ◽  
pp. 51-55
Author(s):  
E N Ostroukhova ◽  
O K Khmel'nitskiĭ ◽  
E I Krasil'nikova ◽  
K S Davidenko
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Adverse Reactions ◽  
Brand Name ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

This paper reports the results of the treatment of 71 patients presenting with type 2 diabetes mellitus using liraglutide, a long-acting analog of glucagon-like peptide-1 (GLP-1) marketed under the brand name Victoza. Practically all the patients experienced either improvement or normalization of the parameters of carbohydrate metabolism in conjunction with a reduction of their body weight and arterial pressure. There were no severe hypoglycemic episodes and other adverse reactions to the therapy. It is recommended that Victoza should be more widely used for the treatment of the patients with type 2 diabetes mellitus.

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