Regulation of Renal Laminin in Mice with Type II Diabetes

Abstract. This study examines the regulation of renal laminin in thedb/dbmouse, a model of type II diabetes characterized by extensive remodeling of extracellular matrix. Immunohistochemistry demonstrated an increase in the contents of laminin chains including β1 chain in the mesangium and tubular basement membranes at 1,2,3, and 4 mo of diabetes. Immunofluorescence with an antibody against the recently discovered laminin α5 chain showed that in the normal mouse, the protein had a restricted distribution to the glomerular and tubular basement membranes with scant expression in the mesangium of older mice. In the diabetic mouse, the laminin α5 chain content of the glomerular and tubular basement membranes was increased, with marked expression in the mesangium. Northern analysis revealed a significantdecreasein the renal cortical contents of α5, β1, and γ1 chain mRNA in the diabetic mice compared to control, at each of the time points.In situhybridization showed decreased abundance of α5 transcripts in the glomeruli of diabetic mice compared to nondiabetic controls. Analysis of mRNA changes by Northern andin situhybridization studies demonstrated that the reduction in laminin transcripts involved both glomerular and tubular elements. These observations demonstrate that laminin accumulation in thedb/dbmice with type II diabetes is due to nontranscriptional mechanisms. Because previous investigations in rodents with type I diabetes have shown that the increase in renal laminin content was associated with a corresponding increment in laminin chain transcript levels, it appears that the mechanisms underlying augmentation in renal matrix laminin content may be distinct in the two types of diabetes.

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Cancer Biology and Prevention in Diabetes

Cells ◽

10.3390/cells9061380 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1380 ◽

Cited By ~ 1

Author(s):

Swayam Prakash Srivastava ◽

Julie E. Goodwin

Keyword(s):

Type Ii Diabetes ◽

Cancer Biology ◽

Cancer Metastasis ◽

Type I Diabetes ◽

Type I ◽

Type Ii ◽

Mesenchymal Transition ◽

Wide Range ◽

Risk Of Cancer

The available evidence suggests a complex relationship between diabetes and cancer. Epidemiological data suggest a positive correlation, however, in certain types of cancer, a more complex picture emerges, such as in some site-specific cancers being specific to type I diabetes but not to type II diabetes. Reports share common and differential mechanisms which affect the relationship between diabetes and cancer. We discuss the use of antidiabetic drugs in a wide range of cancer therapy and cancer therapeutics in the development of hyperglycemia, especially antineoplastic drugs which often induce hyperglycemia by targeting insulin/IGF-1 signaling. Similarly, dipeptidyl peptidase 4 (DPP-4), a well-known target in type II diabetes mellitus, has differential effects on cancer types. Past studies suggest a protective role of DPP-4 inhibitors, but recent studies show that DPP-4 inhibition induces cancer metastasis. Moreover, molecular pathological mechanisms of cancer in diabetes are currently largely unclear. The cancer-causing mechanisms in diabetes have been shown to be complex, including excessive ROS-formation, destruction of essential biomolecules, chronic inflammation, and impaired healing phenomena, collectively leading to carcinogenesis in diabetic conditions. Diabetes-associated epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndMT) contribute to cancer-associated fibroblast (CAF) formation in tumors, allowing the epithelium and endothelium to enable tumor cell extravasation. In this review, we discuss the risk of cancer associated with anti-diabetic therapies, including DPP-4 inhibitors and SGLT2 inhibitors, and the role of catechol-o-methyltransferase (COMT), AMPK, and cell-specific glucocorticoid receptors in cancer biology. We explore possible mechanistic links between diabetes and cancer biology and discuss new therapeutic approaches.

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Plasma endothelin-1 and total insulin exposure in diabetes mellitus

Clinical Science ◽

10.1042/cs0970149 ◽

1999 ◽

Vol 97 (2) ◽

pp. 149-156 ◽

Cited By ~ 9

Author(s):

Flemming WOLLESEN ◽

Lars BERGLUND ◽

Christian BERNE

Keyword(s):

Type Ii Diabetes ◽

Type I Diabetes ◽

Insulin Dose ◽

Albumin Excretion Rate ◽

Wall Structure ◽

Type I ◽

Type Ii ◽

C Peptide ◽

Patients With Diabetes

Insulin stimulates endothelin-1 (ET-1) expression in a dose-response relationship, and ET-1 effects on vascular wall structure are similar to the long-term complications of diabetes. We therefore determined whether the plasma ET-1 concentration in patients with diabetes is associated with their total insulin exposure to see if plasma ET-1 might be a link between insulin exposure and long-term complications of diabetes. We studied 69 patients with Type I and 40 patients with Type II diabetes mellitus in equally tight glycaemic control for 2 years in a cross-sectional design. We measured basal and glucagon-stimulated plasma C-peptide, abdominal sagittal diameter, skinfold thickness, glomerular filtration rate, albumin excretion rate and standard clinical characteristics. Mean HbA1c was 6.4% in Type I and 6.3% in Type II diabetes. Patients with an albumin excretion rate > 300 μg/min were excluded. Adjusted mean plasma ET-1 was 4.11 (S.E.M. 0.39) pg/ml in 21 normal subjects, 3.47 (0.19) pg/ml in Type I diabetes and 4.84 (0.26) pg/ml in Type II diabetes (P = 0.0001). In all patients with measurable plasma C-peptide, plasma ET-1 was associated with basal plasma C-peptide (r = 0.5018, P < 0.0001), with stimulated plasma C-peptide (r = 0.5379, P < 0.0001), and with total daily insulin dose (r = 0.2219, P = 0.00851). Abdominal obesity, metabolic abnormalities, blood pressure and glomerular filtration rate were not associated with plasma ET-1, when corrected for C-peptide and daily insulin dose. Our study shows that the plasma concentration of ET-1 is closely associated with insulin secretion and insulin dose in patients with diabetes. Plasma ET-1 is higher in Type II diabetes than in Type I diabetes. Increased insulin exposure in patients with diabetes may have long-term effects on vascular wall structure through its stimulation of ET-1 expression.

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Type I Diabetes Masquerading as Type II Diabetes: Possible implications for prevention and treatment

Diabetes Care ◽

10.2337/diacare.17.10.1214 ◽

1994 ◽

Vol 17 (10) ◽

pp. 1214-1219 ◽

Cited By ~ 23

Author(s):

R. D. Leslie ◽

P. Pozzilli

Keyword(s):

Type Ii Diabetes ◽

Type I Diabetes ◽

Type I ◽

Type Ii ◽

Prevention And Treatment

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Sitagliptin (Januvia)

Top Drugs ◽

10.1093/oso/9780199362585.003.0012 ◽

2015 ◽

Author(s):

Jie Jack Li

Keyword(s):

Diabetes Mellitus ◽

Blood Glucose ◽

Type Ii Diabetes ◽

Kidney Diseases ◽

Type I Diabetes ◽

Glycosylated Hemoglobin ◽

Insulin Injection ◽

Type I ◽

Type Ii ◽

Ancient Times

Diabetes has been known since antiquity. In fact, the term “diabetes mellitus” comes from the Greek meaning “siphon and honey” due to the excess excretion (siphon or faucet) of hyperglycemic (sweetened, or honeyed) urine associated with diabetes. In ancient times, diabetes was mostly type I, which usually manifests acutely in the young, secondary to certain underlying insults (possibly infections) to the islet cells of the pancreas resulting in an absolute lack of insulin. Insulin was discovered by Banting and Best in 1921, and insulin injection has literally saved millions of lives since then. With the wondrous efficacy that insulin bestows, type I diabetes is largely controlled because type I diabetes is insulindependent. However, type II diabetes, a more prevalent form of diabetes, is not insulin-dependent. In ancient times, when nutrition was scarce and obesity was not prevalent, type II diabetes mellitus (T2DM) was extremely rare. Indeed, type II diabetes is a disease more frequently associated with maturity, obesity, and gradually increasing blood glucose concentrations, and it may be asymptomatic for some time, only discovered on routine glucose screening. In fact, with the increasing body weight of the general population of the developed world, type II diabetes is becoming an epidemic. Serious complications of diabetes include nephropathy (kidney diseases), neuropathy (nerve damage), and retinopathy (blindness). Diabetes is the most common cause of blindness and amputation in the elderly in the United States. Oral diabetes drugs are required for most type II diabetic patients. Diabetes drugs may be classified into four categories: (a) agents that augment the supply of insulin such as sulfonylureas; (b) agents that enhance the effectiveness of insulin such as biguanides and thiazolidinediones; (c) GLP agonists; and (d) DPP4 Inhibitors. The efficacy of all the antidiabetic drugs can be monitored by measuring glycosylated hemoglobin (HaA1c) as a long term marker of elevated blood glucose. The amount of HaA1c reflects the average level over the last 120 days, the life span of a red blood cell, and should remain below 7%.

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PSYCHOLOGICAL FEATURES OF PATIENTS WITH TYPE

10.12731/2658-4034-2021-12-4-2-349-356 ◽

2021 ◽

Author(s):

O. L. Moskalenko ◽

O. V. Smirnova ◽

E. V. Kasparov ◽

I. E. Kasparova

Keyword(s):

Type Ii Diabetes ◽

Type I Diabetes ◽

Psychological Characteristics ◽

Type I ◽

Type Ii ◽

Psychological Techniques ◽

Patients With Diabetes ◽

Psychological Features ◽

Depressive States

The article is devoted to the study of psychoemotional characteristics of patients with diabetes mellitus. Conducting psychological techniques, testing, questioning patients will reveal anxiety-depressive states and psychological characteristics of patients with type I diabetes and type II diabetes for successful disease control. It is necessary to strive for the examination of such patients with an individual approach for each. To improve the quality of life of such patients, it is necessary to search for effective approaches in the education system of patients with type I diabetes and type II diabetes with the participation of psychologists.

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Reviews : Diabetes Stuff and More Stuff: A Book About Type I Diabetes for Young People and Their Families by Twila Okerlund and Virginia Hess (1989); Diabetes Living & Learning: A Book for the Adult With Type I or Type II Diabetes by Twila Okerlund and Virginia Hess (1988). HERC Inc, PO Box 30090, Lincoln, NE 68503. Both booklets are soft cover, 56 pages. Price: $4.25 each

The Diabetes Educator ◽

10.1177/014572179001600606 ◽

1990 ◽

Vol 16 (6) ◽

pp. 460-460

Author(s):

Jessie H. Ahroni

Keyword(s):

Young People ◽

Type Ii Diabetes ◽

Type I Diabetes ◽

Type I ◽

Type Ii

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Impact of concentrations of glycated hemoglobin, α-tocopherol, copper, and manganese on oxidation of low-density lipoproteins in patients with type I diabetes, type II diabetes and control subjects

Clinica Chimica Acta ◽

10.1016/0009-8981(96)06384-x ◽

1996 ◽

Vol 254 (2) ◽

pp. 173-186 ◽

Cited By ~ 14

Author(s):

Wolfgang Leonhardt ◽

Markolf Hanefeld ◽

Grit Müller ◽

Cornelia Hora ◽

Dieter Meissner ◽

...

Keyword(s):

Type Ii Diabetes ◽

Glycated Hemoglobin ◽

Type I Diabetes ◽

Diabetes Type ◽

Low Density Lipoproteins ◽

Type I ◽

Low Density ◽

Type Ii ◽

Diabetes Type Ii ◽

And Control

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Family histories of Type II diabetes and hypertension predict intima–media thickness in patients with Type I diabetes

Diabetologia ◽

10.1007/s00125-002-0817-6 ◽

2002 ◽

Vol 45 (5) ◽

pp. 711-718 ◽

Cited By ~ 20

Author(s):

S. Mäkimattila ◽

K. Ylitalo ◽

A. Schlenzka ◽

M.-R. Taskinen ◽

P. Summanen ◽

...

Keyword(s):

Type Ii Diabetes ◽

Type I Diabetes ◽

Intima Media Thickness ◽

Type I ◽

Type Ii ◽

Media Thickness ◽

Family Histories

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Haemostasis Disturbances in Type I and II Diabetes Mellitus.

Blood ◽

10.1182/blood.v106.11.4032.4032 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4032-4032

Author(s):

Patrick Van Dreden ◽

Aurelie Rousseau ◽

Thomas Exner ◽

Marc Vasse ◽

Geneviéve Ozenne ◽

...

Keyword(s):

Diabetes Mellitus ◽

Pilot Study ◽

Platelet Activation ◽

Type Ii Diabetes ◽

Type I Diabetes ◽

Factor Xa ◽

Diabetic Patients ◽

Type I ◽

Type Ii ◽

Small Pilot Study

Abstract Diabetes is associated with disturbances in haemostasis that are thought to result in an increased incidence of thrombotic complications and cardiovascular disease. The aim of this pilot study was to monitor activation of haemostasis using specific markers for platelet activation and coagulation. Plasma samples (all blood collected and plasma prepared in the same hospital under the same conditions) were obtained from twenty diabetic patients (8 with type I and 12 with type II) and twenty one normal control volunteers. To monitor coagulation these samples were evaluated with the partial thromboplastin time (APTT), prothrombin time (PT) and D-dimer (D-Di) - all reagents from Diagnostica Stago, Asniéres, France. Platelet activation was monitored with a novel method for monitoring procoagulant phospholipids microparticles (PPM) using a factor Xa-based coagulation assay. In this assay shortened clotting times are associated with increased levels of PPM and thus platelet activation. APTT Sec. PT % PPM Sec. D-Di μg/l Controls 34.6 (29.4–39.6) 93.1 (79–109) 57.5 (51.1–74.9) 0.22 (0.22–0.45) Type I Diabetes 34.5 (33.1–36.7) 96.9 (92–102.5) 33.8 (19.1–44.2) 1.6 (0.22–3.6) Type II Diabetes 36.8 (33.2–40.4) 96 (59.4–112.5) 48.3 (44.2–51.2) 0.7 (0.22–1.7) Significantly higher levels of both PPM and DD were found in Type I diabetes patients compared with controls (both P<0.001). In type II diabetes the levels of both were lower than those found in Type I diabetes but both were still higher than the controls (PPM and DDi at p<0.001 and p<0.01 level respectively), only the differences in levels of PPM reaching significance between type I and type II diabetes (p<0.01). The more severe the diabetes (type I > type II) the greater the level activation of haemostasis that is observed. The increases in PPM could account in part for the development or progression of arthrosclerosis in patients with diabetes mellitus. The increased level of D-Di confirms the increased hypercoagulability of these patients. Although this was a small pilot study and further studies are needed to confirm these findings it is interesting to speculate on the usefulness of both the PPM assay and D-Di assays in monitoring the development/severity of diabetes and its complications. The PPM assay may prove to be especially useful in monitoring progression of the disease.

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