Subcellular distribution of GLUT 4 in the skeletal muscle of lean type 2 (non-insulin-dependent) diabetic patients in the basal state

Summary Insulin resistance of the skeletal muscle is a key feature of Type 2 (non-insulin-dependent) diabetes mellitus. To determine whether a decrease of glucose carrier proteins or an altered subcellular distribution of glucose transporters might contribute to the pathogenesis of the insulin resistant state, we measured glucose transporter numbers in membrane fractions of gastrocnemius muscle of 14 Type 2 diabetic patients and 16 non-diabetic control subjects under basal conditions. Cytochalasin-B binding and immunoblotting with antibodies against transporter-subtypes GLUT 1 and GLUT 4 were applied. The cytochalasin-B binding values (pmol binding sites/g muscle) found in a plasma membrane enriched fraction, high and low density membranes of both groups (diabetic patients and non-diabetic control subjects) suggested a reduced number of glucose transporters in the plasma membranes of the diabetic patients compared to the control subjects (diabetic patients: 1.47 ± 1.01, control subjects: 3.61 ± 2.29,p ≤ 0.003). There was no clear difference in cytochalasin-B binding sites in high and low density membranes of both groups (diabetic patients: high density membranes 3.76 ± 1.82, low density membranes: 1.67 ± 0.81; control subjects: high density membranes 5.09 ± 1.68, low density membranes 1.45 ± 0.90). By Western blotting analysis we determined the distribution of the glucose transporter sub-types GLUT 1 and GLUT 4 in the plasma membrane enriched fraction and low density membranes of seven patients of each group. In agreement with the cytochalasin-B binding data and despite a high variance within one group, the results show a clear decrease of GLUT 4 in the plasma membrane enriched fraction of diabetic patients compared to control subjects. In contrast, we found no difference in the distribution of GLUT 1 in diabetic patients and control subjects. In conclusion, despite a high variance of glucose transporter numbers in the skeletal muscle of different individuals fractionation of muscle samples clearly suggests that the number of GLUT 4 is reduced in the plasma membrane fraction of skeletal muscle of lean diabetic patients in the basal state.     

Enhancement of B-cell secretion by blood glucose normalization in type 2 diabetes is associated with fasting C-peptide levels

OBJECTIVES: To investigate (i) the variability of beneficial effects achieved by short-term near-normalization of blood glucose in type 2 diabetes patients, and (ii) the relationship of beneficial effects to individual characteristics of diabetes. DESIGN: Arginine-induced insulin and glucagon release tested at two glucose levels before and after 3 days of intensive insulin treatment. SETTING: The Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm, Sweden. SUBJECTS: Type 2 diabetes patients with poor metabolic control sampled from an area-based population of diabetes patients. RESULTS: Levels of fasting blood glucose declined from 15.0 +/- 0.9 to 8.5 +/- 0.7 mmol L-1, C-peptide from 0.81 +/- 0.06 to 0.49 +/- 0.05 nmol L-1 and percent proinsulin (of total IRI) from 7.8 +/- 1.0 to 3.2 +/- 0.6%. At comparable glucose levels arginine-induced insulin secretion was enhanced 46.3 +/- 19.5% (range -36 to 220%). Enhancement correlated with extent of blood glucose normalization and also with fasting C-peptide levels and with overweight. Arginine-induced glucagon secretion was nonsignificantly depressed (17.2 +/- 7.4%, range -59 to 29%). Insulin sensitivity assessed by M:I ratio was increased by a median of 95%. CONCLUSIONS: In type 2 diabetes patients reversibility of the effects of poor metabolic control on B-cell function is variable. Variability is related to B-cell mass in individual patients with type 2 diabetes.     

Fetal pancreatic Langerhans islets size in pregnancies with metabolic disorders

Objective: Metabolic disorders are a pandemic and increasing health problem. Women of childbearing age may also be affected, thus an abnormal metabolism may interfere with pregnancy short- and long-term outcomes, harming both mother and child. In the context of an abnormal maternal and intrauterine metabolic milieu the development of fetal organs, including pancreas, may be affected.

Aim: To investigate the effects of pregnancy metabolic disorders on the morphology of pancreatic Langerhans islets in human late-third trimester stillborn fetuses.

Methods: Samples from fetal pancreas underwent a quantitative histological evaluation to detect differences between pregnancy with (cases, n?=?9) or without (controls, n?=?6) abnormal metabolism.

Results: Results show that the islets size increases in fetuses from dysmetabolic pregnancies and that this increment is related to both beta-cell hyperplasia and hypertrophy. Moreover, according to pregnancy and fetal metabolic disorders, a threshold of abnormal size of the islets has been identified. Above this threshold the size of fetal pancreatic Langerhans islets should be considered excessively increased.

Conclusion: The study suggests that an accurate fetal pancreas analysis supplies an important tool in stillborn fetus, to discover metabolic disturbances that should be kept in mind and managed in future pregnancies.     

Commentary: SGLT inhibitors in type 1 diabetes: Place in therapy and a risk mitigation strategy for preventing diabetic ketoacidosis - the STOP DKA protocol

In the accompanying article, Goldenberg et al. review the promotion of diabetic ketoacidosis by SGLT2 inihibitors. They have carried out a metanalysis showing a 3.5-fold increase in the risk of diabetic ketoacidosis (DKA) in patients with type 1 diabetes under treatment with SGLT2 inhibitors. They make a number of suggestions for attempting to mitigate the risk of DKA in these patients, notably including blood ketone monitoring and the use of supplemental carbohydrates with additional insulin when ketones suggest incipient DKA. Their proposal merits evaluation in a clinical trial involving type 1 diabetes, which should also assess the possible cardiorenal benefits demonstrated with treatment with SGLT2 inhibitors in type 2 diabetes.     

理气中药组方对糖尿病大鼠胃排空延迟的作用

目的:观察理气中药经验组方对糖尿病大鼠胃排空延迟的干预作用。方法:雌雄各半成年SD大鼠110只,随机分为正常组(A组)、糖尿病中药组(B组)、糖尿病胃复安组(C组)、糖尿病组(D组)。A组、D组1次/d按10 mL/只予0.9%生理盐水灌胃,B组1次/d按8 mL/只予中药煎剂灌胃,C组1次/d按0.5 mg/只予胃复安片灌胃。喂养12周后,行13C胃排空实验及甲基橙水溶液胃排空实验,观察各组大鼠胃排空情况。结果:糖尿病大鼠胃排空较正常大鼠明显延迟(P0.01),糖尿病大鼠胃排空延迟模型制作成功。糖尿病中药组和糖尿病胃复安组大鼠胃排空较糖尿病组快(P0.01);糖尿病中药组大鼠胃排空较糖尿病胃复安组大鼠快(P0.05)。结论:常规喂养12周后糖尿病大鼠出现胃排空延迟。理气中药陈皮、枳实、木香、香附组方煎剂和胃复安均能促进糖尿病大鼠胃排空,理气中药组方煎剂的效果优于胃复安。     

Dexmedetomidine enhances ropivacaine-induced sciatic nerve injury in diabetic rats

Background

Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown.

Vegetarians have a lower fasting insulin level and higher insulin sensitivity than matched omnivores: A cross-sectional study

Background and aims

Potential associations of vegetarian diet patterns with fasting insulin (FI) and insulin sensitivity remain unclear. We aimed to investigate whether vegetarian diets were associated with FI and insulin sensitivity in a cross-sectional study in Chinese vegetarians and matched omnivores and then to test whether it is independent of body mass index (BMI).