Plant- and Nutraceutical-based Approach for the Management of Diabetes and its Neurological Complications: A Narrative Review

: Diabetes is an important metabolic disease affecting many organs and systems in the body. The nervous system is one of the body systems affected by diabetes and neuropathic complications are troublesome in diabetic patients with many consequences. As diabetes has deleterious influences almost on bodily systems, an integrative approach seems to be necessary accepting the body as a whole and integrating body systems with lifestyle and living environment. Like some traditional health systems such as Ayurveda, integrative approach includes additional modalities to overcome both diabetes and diabetic complications. In general, these modalities consist of nutraceuticals and plant products. Prebiotics and probiotics are two types of nutraceuticals having active ingredients, such as antioxidants, nutrient factors, microorganisms, etc. Many plants are indicated for the cure of diabetes. All of these may be employed in the prevention and in the non-pharmacological management of mildto- moderate diabetes. Severe diabetes should require appropriate drug selection. Being complementary, prebiotics, probiotics, plants and exercise may be additive for the drug therapy of diabetes. Similarly, there are complementary approaches to prevent and cure neurological and/or behavioral manifestations of diabetes, which may be included in therapy and prevention plans. A scheme is given for the prevention and therapy of comorbid depression, which is one of the most common behavioral complications of diabetes. Within this scheme, the main criterion for the selection of modalities is the severity of diseases, so that personalized management may be developed for diabetic patients using prebiotics and probiotics in their diets, plants and drugs avoiding possible interactions.

Tubular sodium handling and tubuloglomerular feedback in experimental diabetes mellitus

Tubular Na handling and tubuloglomerular feedback (TGF) activity were assessed using micropuncture techniques during the hyperfiltration phase of streptozotocin-induced diabetes mellitus in Sprague-Dawley rats. Three animal groups were studied, designated as having severe diabetes [blood sugar level (BSL) 18-25 mmol/l], moderate diabetes (BSL 13-18 mmol/l) and control (BSL less than 10 mmol/l). Single-nephron glomerular filtration rate (SNGFR) measured at both late proximal (LP) and early distal (ED) sites was elevated in severe diabetes compared with both other groups. TGF activity, determined as the difference between LP and ED measurements of SNGFR, was significantly increased in severe diabetes (46.4 +/- 6.6 vs. 30.1 +/- 6.5 vs. 14.8 +/- 1.9 nl/min). Tubular Na transport was higher in severe diabetes compared with control, as demonstrated by a decrease in fractional delivery of Na to the LP (42.9 +/- 3.0 vs. 52.9 +/- 1.9%), as well as to the ED site (4.5 +/- 0.4 vs. 12.3 +/- 0.9%). Administration of phlorizin to severely diabetic animals resulted in a BSL comparable to that observed in moderate diabetes, and whole animal GFR, as well as SNGFR, TGF activity, and tubular Na handling were also similar to those found in moderate diabetes. Studies performed during mannitol infusion demonstrated that osmotic diuresis alone was not associated with the changes in TGF and tubular Na handling observed in the diabetic state. These data suggest that the hyperfiltration occurring in early diabetes is associated with enhanced proximal and loop resorption of Na independent of Na-glucose cotransport and osmotic diuresis. Activation of TGF serves to limit the rise in GFR, which results from factors as yet unrecognized in the diabetic state.

Metabolic regulation of somatomedin activity in rat liver

ABSTRACT We have compared circulating and hepatic somatomedin (SM) activity in rats with diabetes or malnutrition of varying severity. Somatomedin activity was measured by the hypophysectomized rat costal cartilage bioassay. In both moderate diabetes and moderate malnutrition, mean serum SM activity was not significantly lower than normal (79 ± 13% (s.e.m.) and 95 ± 11% vs normal controls respectively). In contrast, liver perfusate SM activity was significantly reduced in both groups (51 ± 12% for moderate diabetes and 44 ± 12% for moderate malnutrition). Liver extract SM activity was also significantly decreased in both moderate diabetes and malnutrition (74 ± 4% and 75 ± 6% vs normal controls respectively). In severe diabetes and malnutrition, both liver and serum activities were low, consistent with previous reports. Our studies showed that liver SM activity fell in response to metabolic stress before a decrease in circulating levels occurred, supporting the concept that the liver regulates serum SM activity and growth in diabetes and malnutrition. J. Endocr. (1984) 101, 257–261

Vascular responsiveness and serum biochemical parameters in alloxan diabetes mellitus

Responses of isolated aorta and portal vein (PV) to norepinephrine (NE), angiotensin II (AII), KCl, and CaCl2 were investigated in alloxan diabetic rats. Based on serum biochemical parameters (i.e., glucose, cholesterol, triglycerides, and creatinine) (alloxan, 150 mg/kg), diabetic rates were divided into three groups: 1) mildly diabetic at 1 week (only elevated glucose levels), 2) moderately diabetic at 4 wk (elevated glucose, triglycerides, and creatinine), and 3) severely diabetic at 8 wk (all serum biochemical parameters elevated). The sensitivity (i.e., ED50) of aortic smooth muscle from diabetic rats when compared to saline controls was 1) unchanged in mild diabetes; 2) decreased to KCl, AII, and CaCl2 in moderate diabetes; and 3) decreased to KCl, NE, and CaCl2 in severe diabetes. Ability of aortic smooth muscle to develop maximal contractions (i.e., contractility) to all these agonists was markedly diminished in severe diabetes. Spontaneous phasic contractions of PV from diabetic rats exhibited progressively greater tension as the disease advanced. Unlike aortas, contractility of PV to vasoactive agents was not affected at any stage of diabetes. PV sensitivity to AII in moderate diabetes and to Ca in severe diabetes was decreased when compared to saline controls. These differences in reactivity and contractility of aorta and PV in progressive stages of experimental diabetes could be due to alterations in calcium handling and its metabolism in arterial and venous smooth muscle cells in the diabetic state.

Lack of adaptation of pancreatic colipase in rats and mice.

A new automated potentiometric method for the determination of colipase was developed, taking advantage of the reactivation of purified lipase, in the presence of bile salt and at pH 6.5. High-fat and high-starch diets induced an opposite regulation of lipase and amylase in the rat pancreas. At the same time, the level of colipase was not influenced by nutrition. During fasting and in alloxan diabetes, the specific activity of lipase almost doubled, that of amylase decreased sharply, and colipase was not affected in the rat pancreas. In obese-hyperglycemic mice, suffering from obesity, hyperinsulinism, and moderate diabetes, there was also no regulation of pancreatic colipase. Thus, at variance with a number of hydrolases, there was no dietary or hormonal adaptation of colipase. However, this was probably without any bearing on intraluminal lipolysis. Indeed, comparison of lipase and colipase activities in pancreas and in small intestine suggests that colipase concentration is not a limiting factor of intraluminal lipolysis. The molecular mechanism of this assumption is discussed on the basis of in vitro studies.