Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion

Emi, Akiko; Pulong, Wijang Pralampita; Marchianti, Ancah Caesarina Novi; Nakakuma, Miwa; Abe, Masaharu; Ushikai, Miharu; Horiuchi, Masahisa

doi:10.1007/s00394-015-1075-y

Cited by 5 publications

(9 citation statements)

References 31 publications

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“…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].…”

Section: Main Outcomesmentioning

confidence: 99%

“…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.…”

Section: Plos Onementioning

confidence: 99%

“…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].…”

Section: Plos Onementioning

confidence: 99%

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

et al. 2020

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Type 2 diabetes mellitus (T2DM) is among the most prevalent diseases in the world, affecting over 420 million people. The disease is marked by a poor metabolic effect of insulin leading to chronic hyperglycaemia, which can result in microvascular complications. It is widely known that postprandial glycaemia is reliant on the total carbohydrate content of a meal. However, the importance of the amount and the source of these carbohydrates remains controversial due to mechanisms other than insulin secretion. Oxidative stress, inflammation, pyruvate production and the quality of the intestinal microbiota, resulting in plasma lipopolysaccharides and short-chain fatty acids production, play an important role in blood sugar control and consequently in type 2 diabetes. Thus, we systematically reviewed the preclinical evidences on the impact of the amount and type of carbohydrate found in different diets and its influence on blood glucose levels in diabetic animals. We used a comprehensive and structured search in biomedical databases Medline (PubMed), Scopus and Web of Science, recovering and analyzing 27 original studies. Results showed that sucroserich diets deteriorated diabetic condition in animal models regardless of the total dietary carbohydrate content. On the other hand, fiber, particularly resistant starch, improved blood glucose parameters through direct and indirect mechanisms, such as delayed gastric emptying and improved gut microbiota. All studies used rodents as animal models and male animals were preferred over females. Improvements in T2DM parameters in animal models were more closely related to the type of dietary carbohydrate than to its content on a diet, i. e., resistant starch seems to be the most beneficial source for maintaining normoglycemia. Results show that current literature is at high risk of bias due to neglecting experimental methods.

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Section: Main Outcomesmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

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

et al. 2020

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“…Of them, db mice are deficient in the leptin receptor and show retinopathy and nephropathy caused by type 2 diabetes (24)(25)(26). The diabetic nephropathy and glucose metabolism abnormality in db mice are aggravated by a high protein content diet (21,22). In the present study, db mice were used to evaluate the effects of dietary protein and carbohydrate content on diabetic retinopathy.…”

Section: Discussionmentioning

confidence: 99%

“…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…”

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confidence: 99%

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

Emi

Okatani

Araki

et al. 2018

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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

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In vivo antidiabetic activity of nimesulide due to inhibition of amino acid transport

Joharapurkar

Kshirsagar

Patel

et al. 2021

Basic Clin Pharma Tox

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Inhibiting the intestinal and renal neutral amino acid transporter B0AT1 by genetic means has improved insulin sensitivity in mice, but there are no antagonists available for preclinical or clinical use. Since the anti‐inflammatory agent nimesulide selectively inhibited B0AT1 in vitro, we hypothesized that nimesulide exhibits in vivo potential to restrict neutral amino acid absorption and, therefore, may improve insulin sensitivity. The dose‐related effect of nimesulide (10 to 100 mg/kg, PO) on intestinal absorption of neutral amino acids was estimated in C57 mice. The effect of nimesulide (50 mg/kg, PO) on renal resorption of amino acids was also assessed. The effect of chronic nimesulide (50 mg/kg, PO, BID for 14 days) was assessed in high protein diet‐fed C57 mice, diet‐induced obese mice and obese and diabetic db/db mice. Acute and chronic nimesulide treatment decreased absorption of neutral amino acids and increased their urinary excretion. Nimesulide treatment improved insulin sensitivity and glycemic control, increased GLP‐1, decreased liver lipids and improved FGF‐21 in serum. Nimesulide improved insulin sensitivity and glucose tolerance by inhibiting neutral amino acid transport in the intestine and kidneys. Thus, it can serve as a tool compound for in vivo B0AT1 inhibition.

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Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion

Abstract: High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.

Cited by 5 publications

References 31 publications

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

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

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

In vivo antidiabetic activity of nimesulide due to inhibition of amino acid transport

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