Vaag A, Alford F, Beck-Nielsen H
Odense University Hospital, Department of Endocrinology and Internal Medicine M, Denmark.
Diabet Med. 1996 Sep;13(9):806-15. doi: 10.1002/(SICI)1096-9136(199609)13:9<806::AID-DIA179>3.0.CO;2-5.
Intracellular glucose and lipid metabolism was studied in 12 identical twin pairs discordant for non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 13 control subjects without family history of diabetes during low (baseline) and high plasma insulin concentrations, using the hyperinsulinaemic clamp technique combined with indirect calorimetry, tritiated water glycolytic flux rates and biopsy skeletal muscle glycogen synthase activity determinations. Baseline and insulin stimulated rates of lipid oxidation were elevated--and glucose oxidation decreased--in the NIDDM twins compared with the non-diabetic co-twins and controls (all p < 0.05). Baseline and insulin stimulated rates of glucose and lipid oxidation were similar in non-diabetic twins and controls. Exogenous glycolytic flux was decreased in NIDDM twins compared with both their non-diabetic co-twins and controls during clamp insulin measurements (p < 0.02), but similar in all study groups during baseline measurements. Insulin stimulated glucose disposal, exogenous glucose storage (glucose disposal-exogenous glycolytic flux) and skeletal muscle glycogen synthase activity were all significantly decreased in NIDDM twins compared with both their non-diabetic co-twins and controls. Furthermore, glucose disposal and glucose storage were decreased in the non-diabetic twins (n = 12) compared with controls (p < 0.05 both). However, insulin stimulated fractional skeletal muscle glycogen synthase activity was not significantly decreased in non-diabetic twins compared with controls.
(1) the glucose fatty acid cycle plays a major role in the secondary--but not the primary--abnormalities of glucose metabolism in NIDDM; (2) insulin resistance in non-diabetic identical co-twins of NIDDM patients is restricted exclusively to the pathway of exogenous glucose storage; (3) however, the decreased glucose storage is not explained solely by an impairment of insulin stimulated skeletal muscle glycogen synthase activity; and finally (4) the impairment of skeletal muscle glycogen synthase activity in NIDDM has an apparent non-genetic component and can be escaped (or postponed) in individuals (twins) with a 100% genetic predisposition to NIDDM.
采用高胰岛素钳夹技术结合间接测热法、氚水糖酵解通量率和活检骨骼肌糖原合酶活性测定，在12对非胰岛素依赖型（2型）糖尿病（NIDDM）不一致的同卵双胞胎以及13名无糖尿病家族史的对照受试者中，研究了低（基线）和高血浆胰岛素浓度下的细胞内葡萄糖和脂质代谢。与非糖尿病双胞胎和对照相比，NIDDM双胞胎的基线和胰岛素刺激的脂质氧化率升高，而葡萄糖氧化率降低（所有p<0.05）。非糖尿病双胞胎和对照的基线和胰岛素刺激的葡萄糖和脂质氧化率相似。在钳夹胰岛素测量期间，与非糖尿病双胞胎和对照相比，NIDDM双胞胎的外源性糖酵解通量降低（p<0.02），但在基线测量期间所有研究组相似。与非糖尿病双胞胎和对照相比，NIDDM双胞胎的胰岛素刺激的葡萄糖处置、外源性葡萄糖储存（葡萄糖处置-外源性糖酵解通量）和骨骼肌糖原合酶活性均显著降低。此外，与对照相比，非糖尿病双胞胎（n = 12）的葡萄糖处置和葡萄糖储存降低（两者p<0.05）。然而，与对照相比，非糖尿病双胞胎的胰岛素刺激的骨骼肌糖原合酶活性分数没有显著降低。
（1）葡萄糖脂肪酸循环在NIDDM葡萄糖代谢的继发性而非原发性异常中起主要作用；（2）NIDDM患者非糖尿病同卵双胞胎的胰岛素抵抗仅局限于外源性葡萄糖储存途径；（3）然而，葡萄糖储存减少并不能仅通过胰岛素刺激的骨骼肌糖原合酶活性受损来解释；最后（4）NIDDM中骨骼肌糖原合酶活性受损具有明显的非遗传成分，并且在具有100%NIDDM遗传易感性的个体（双胞胎）中可以避免（或推迟）。
