Effects of Diets with Different Proportions of Protein/ Carbohydrate on Retinal Manifestations in db Mice

Abstract

Abstract. Background Diabetic retinopathy is one of the three major complications of diabetes, and it is the leading cause of visual impairment and blindness among adults (1). A recent epidemiological study found diabetic retinopathy prevalence to be 34.6% for individuals with diabetes (2). In the Wisconsin Epidemiological Study of Diabetic Retinopathy, microalbuminuria, representing nephropathy, was associated with the presence of retinopathy in individuals with diabetes (3). The recent rise in the numbers of diabetes and diabetic retinopathy cases worldwide is likely to be related to lifestyle/life environment rather than genetic factors, as a global genetic diversity has not changed appreciably over this short period of time (4-7). Lifestyle factors, including nutrition, have been altered markedly in recent decades (8, 9). Diabetic nephropathy is aggravated by higher intake of total protein (10, 11). However, the impact of altered nutrition, especially protein content, on the development of diabetic retinopathy is not fully understood (10,11,12).Glycemic control and blood pressure control reduce the progression of diabetic retinopathy, and ophthalmological treatment including laser applications plays a prominent role in the control of diabetic retinopathy. However, currently there are no drugs that inhibit the onset or progression of diabetic retinopathy, except for inhibitors of the renin-angiotensin (RA) system (13-17). Regarding nutritional intervention, patients with diabetic retinopathy have been managed by a low-energy diet of suppressed carbohydrate intake and relatively highprotein intake, but the influence of diet on the pathophysiology of retinopathy is not fully understood. A rodent study of diabetic nephropathy reported an additive effect of RA system inhibitors and a low-protein diet on kidney manifestations (18). A low-protein diet may have additional beneficial effects through suppressed expression of genes involved in the kidney RA system. The effect of dietary protein content diets (12-24% energy), which is the range in regular human diets (4, 8), on glucose levels and renal manifestations in db mice (19,20), an animal model for diabetes with leptin-receptor deficiency. In the experiments using db mice, a high-protein, low-carbohydrate diet increased blood glucose levels and exacerbated renal manifestations, compared with a low-protein, high-carbohydrate diet (21,22). The dietary protein content should be examined for its 265

Increased Expression of Ecto-NOX Disulfide-thiol Exchanger 1 (ENOX1) in Diabetic Mice Retina and its Involvement in Diabetic Retinopathy Development

“…T2D mouse model. T2D mice (BKS.Cg-Dock7 m +/+Lepr db /JNarl, abbreviation db/db), and their non-diabetic littermates (control mice, abbreviation +/+) were obtained from the National Laboratory Animal Center (Taipei, Taiwan) (16,17). Six male mice per group were grown for 32 weeks during the experiment (15).…”

Effects of the amount and type of carbohydrates used in type 2 diabetes diets in animal models: A systematic review

“…Eighteen studies reported a worsening in blood glucose parameters; six of them intervened with a high carbohydrate diet [23][24][25][26][27][28]. One study intervened with a very high carbohydrate high fiber diet [29] and 3 studies intervened with a very high carbohydrate diet [30][31][32]. Six articles reported worsened blood glucose parameters under low carbohydrate diets [33][34][35][36][37][38] and 2 under moderate carbohydrate diets [39,40].…”

“…High carbohydrate diets increased body weight in all studies, particularly when the main carbohydrate source was sucrose. In the absence of fiber, both low-carbohydrate diets [34][35][36][37][38] and high-carbohydrate diets [24,28,31,32] led to increased insulin secretion. Similarly, both low- [35,36] and high-carbohydrate diets [26,27,30] resulted in decreased glucose tolerance when no fiber was available in the diet.…”

“…The main mechanisms involved with carbohydrate intake that impair T2DM parameters were increased pyruvate production leading to fatty liver and increased serum lipids leading to metabolic syndrome [23, 24, 26-30, 33-38, 40]. Three studies reported a worsening in T2DM parameters unrelated to these mechanisms [20,31,32]. Improvements in T2DM parameters were associated with prebiotic effects of fiber and resistant starch, increased satiety and increased gastrointestinal transit time [21,22,39,45].…”

Higher Branched-chain Amino Acids and Lower Serine Exist in the Plasma of Nondiabetic Mice: A Comparison Between High- and Low-protein Diet Conditions

“…The effects of dietary protein content on the complications of type 2 diabetes have also been shown in animals (8)(9)(10)(11). We showed that mice with type 2 diabetes that consume a high-protein diet and are pair-fed according to the energy and fat intake of control mice demonstrate more rapid deteriorations in their diabetic and renal phenotypes than db mice fed a low-protein diet (9).…”